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EC number: 201-143-3 | CAS number: 78-79-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
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- Nanomaterial pour density
- Nanomaterial photocatalytic activity
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- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Carcinogenicity
Administrative data
Description of key information
There is clear evidence of carcinogenicity of isoprene in mice, with increases in the incidence of malignant neoplasms in the liver, lung, Harderian gland and forestomach. Histiocytic sarcomas and haemangiosarcomas were also observed, together with benign tumours observed in the liver, lung, Harderian gland, forestomach and pituitary.
In rats, there were no significant increases in the incidence of malignant tumours, although isoprene exposures were associated with increases in benign tumours of the testes, kidney and mammary gland.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via inhalation route
Link to relevant study records
- Endpoint:
- carcinogenicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, near guideline study, published in peer reviewed literature, fully reliable for assessment
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPP 83-2 (Carcinogenicity)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River's Portage Laboratory
- Age at study initiation: no older than 10 weeks
- Housing: individually housed in stainless steel wire-mesh inhalation cages that fitted into the exposure chambers
- Diet: Certified Purina Rodent Chow in pellet form ad libitum except during exposure
- Water: ad libitum except during exposure
- Acclimation period: 25 days
- Prior to the study, sera were collected from at least 5 mice/sex and were found free of antibody titers to common murine pathogens.
ENVIRONMENTAL CONDITIONS
- Temperature: 22±2°C (chamber)
- Humidity: 40-70% (chamber)
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: no data - Route of administration:
- inhalation: vapour
- Vehicle:
- other: air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: exposure chambers (Hazelton H1000 or H2000, 1000 or 2000 L in volume)
- Method of holding animals in test chamber: stainless steel wire-mesh cages
- Test atmospheres were generated from the liquid as an aerosol by ultrasonic nebulization followed by evaporation in a stainless steel aging plenum
- Filtered compressed air was supplied to the ultrasonic spray nozzle. Isoprene was fed to the spray nozzle from the storage cylinder which was pressurized with N2 at 5 psig.
- Room air was drawn into the aging plenum through charcoal and high efficiency particulate air (HEPA) filters and carried isoprene vapour to the exposure chambers through a common distribution manifold with subsequent dilution at each chamber to the target concentrations.
- Temperature: 22±2°C (range:22.1 to 22.7°C); humidity 40-70% (range: 52.3 to 55.0%)
- Chamber flow was a nominal 15 air changes per h
- Chamber pressure and flowrate were monitored continuously during exposures
TEST ATMOSPHERE
- Brief description of analytical method used: A Miran-980 infrared spectrometer (IR) was used to measure isoprene concentrations in the chambers and exposure room.
- An hourly sampling sequence was used to minimize the step change in concentration among chambers.
- Some chamber samples were also analyzed with a gas chromatograph with a Flame Ionization Detector, primarily to determine the concentrations of limonene (isoprene dimer).
- Uniformity within the exposure chambers was verified by measuring the isoprene concentration at the front, middle, and back of each chamber level.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Buildup and decay of isoprene in the chambers were rapid with T90 achieved in 4 to 10 min. Using an aerodynamic particle size (APS 338; TSI, Inc., St. Paul, MN, USA), no residual aerosol was detected during vapour generation.
All values were within 4% of target concentrations. - Duration of treatment / exposure:
- 4 or 8 hours/day
- Frequency of treatment:
- variable - 5 days/week for 20, 40 or 80 weeks
- Remarks:
- Doses / Concentrations:
0, 10, 70, 140, 280, 700 or 2200 ppm
Basis:
nominal conc.
4 hr - Remarks:
- Doses / Concentrations:
0, 28, 195, 390, 780, 1950, 6129 mg/m3
Basis:
nominal conc. - Remarks:
- Doses / Concentrations:
10.4, 70.1, 141, 280, 700 or 2173 ppm
Basis:
analytical conc.
grand means (4 h) - Remarks:
- Doses / Concentrations:
2203 ppm
Basis:
analytical conc.
grand mean (8 h) - No. of animals per sex per dose:
- 50
- Control animals:
- yes, sham-exposed
- Details on study design:
- Post-exposure period: variable - animals held following exposures until week 96 or 105
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly for 13 weeks and then monthly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly for 13 weeks and then monthly
HAEMATOLOGY: Yes
- Blood samples were collected using EDTA-containing tubes from the retro-orbital sinus from each animal reaching scheduled necropsy.
- The following parameters were measured: red blood cell count, haematocrit, haemoglobin, total white blood cell count and white blood cell differential and morphology evaluation.
OTHER: Micronucleus evaluation:
- Evaluations of peripheral blood were performed on 10 animals per exposure group using samples obtained the day after the last exposure for those groups ending exposure after 40 and 80 weeks. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- A complete gross necropsy was performed on all animals that died during the study or at scheduled necropsy
- Animals were anaesthetized using pentobarbital and exsanguinated
- Tissues from all major organs were removed and preserved in 10% neutral buffered formalin, except for the eyes and testes which were fixed in Bouin's solution.
HISTOPATHOLOGY: Yes
- Histopathological evaluations were conducted on all tissues from all animals, including early death or moribund-sacrificed animals.
- Tissues were embedded in paraffin, sectioned at approximately 5 µm, stained with haematoxylin and eosin and the slides evaluated by light microscopy. - Statistics:
- Body weights, organ weights and haematology data were evaluated by analysis of variance (ANOVA) followed by Duncan's new multiple range test. Incidences of tumour types were analyzed using Fischer's exact test applied to each combination of exposure group and tumour type.
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Details on results:
- CLINICAL SIGNS AND MORTALITY
There was an isoprene concentration-related effect on survival. At approximately Week 80, animals exposed to higher concentrations (280 to 2200 ppm, Groups 7 through 12) had lower survival rates (< 50%) than the controls or animals exposed to less than 280 ppm for 80 weeks.
GROSS PATHOLOGY
Gross lesions considered to be directly or in directly related to isoprene exposure were observed in the eyes, forestomach, Harderian gland, liver, lung, spleen, mesenteric lymph node, and testis of male and, in general, correlated with the histopathological findings.
HISTOPATHOLOGY:
Eyes were opaque and often protruded due to enlarged Harderian glands. The forestomach, when affected, had small nodules on the mucosal surface and two isoprene-exposed mice had forestomach masses. The incidences of liver nodules and masses were increased in higher isoprene exposure-level concentration groups compared to controls, as were the incidences of lung nodules and masses. The number of enlarged spleens was slightly increased at higher isoprene exposure-levels, as was the incidence of enlarged mesenteric lymph nodes. The incidence of small testes was increased at exposures above 5600 ppm-weeks (concentration times exposure-weeks).
ORGAN WEIGHT
Absolute testis, testis-to-body weight ratio and testis-to-brain weight ratio values were significantly less (20 to 30%) in Groups 7, 8, 10, and 12 compared to controls.
Heart weight was significantly less in 10 ppm females but not at 70 ppm. Mean ovary weight was less, although not significantly, in 10 and 70 ppm
females compared to controls. The lower gonadal weights may have been exposure-related.
NON-NEOPLASTIC CHANGES
Numerous non-neoplastic lesions were observed. There was a slight increase in alveolar epithelial lining cell hyperplasia at the higher doses in male mice. Focal areas of epithelial hyperplasia of the forestomach mucosa were observed more often in males at the higher levels of isoprene. The nose/nasal cavity had a significant non-neoplastic lesion that was more prominent in the four highest doses in males and the highest dose in females. The lesion was in the dorsal meatus and consisted of focal areas of mild metaplasia of the olfactory epithelium to respiratory epithelium. The metaplastic epithelium often in-vaginated to form glandular patterns.
NEOPLASTIC CHANGES
Several types of neoplasms occurred only, or in greater frequency, in mice exposed to isoprene compared to controls. - Dose descriptor:
- NOEC
- Effect level:
- 28 mg/m³ air (nominal)
- Sex:
- male/female
- Remarks on result:
- other: Effect type: carcinogenicity
- Dose descriptor:
- LOEC
- Effect level:
- 1 950 mg/m³ air (nominal)
- Sex:
- male
- Basis for effect level:
- other: lung tumour and haemangiosarcoma
- Remarks on result:
- other: Effect type: carcinogenicity
- Dose descriptor:
- LOEC
- Effect level:
- 780 mg/m³ air (nominal)
- Sex:
- male
- Basis for effect level:
- other: malignant forestomach tumours and histiocytic sarcomas
- Remarks on result:
- other: Effect type: carcinogenicity
- Dose descriptor:
- LOEC
- Effect level:
- 390 mg/m³ air (nominal)
- Sex:
- male
- Basis for effect level:
- other: liver tumours
- Remarks on result:
- other: Effect type: carcinogenicity
- Dose descriptor:
- LOEC
- Effect level:
- 195 mg/m³ air (nominal)
- Sex:
- male
- Basis for effect level:
- other: Harderian gland tumours
- Remarks on result:
- other: Effect type: carcinogenicity
- Dose descriptor:
- LOEC
- Effect level:
- 195 mg/m³ air (nominal)
- Sex:
- female
- Basis for effect level:
- other: possible haemagiosarcomas
- Remarks on result:
- other: Effect type: carcinogenicity
- Conclusions:
- The results of this study indicated that concentration, length of daily exposure, and weeks of exposure did not affect tumour incidence equivalently and total cumulative exposure was not sufficient for predicting oncogenic risk from isoprene exposure in mice. There appeared to be threshold for oncogenic effects in mice, which varied by organ and tumour type. For male mice, the LOEC was 700 ppm (1950 mg/m3) for lung tumour and haemangiosarcoma, 280 ppm (780 mg/m3) for malignant forestomach tumours and histiocytic sarcomas, 140 ppm (390 mg/m3) for liver tumours, and 70 ppm (195 mg/m3) for Harderian gland tumours. For female mice, the LOEL was 70 ppm for total non-liver, non-lung adenomas and possibly for haemagiosarcomas.
- Executive summary:
Groups of mice were exposed to isoprene 8 hr/day, 5 days/week at concentrations of 0, 10, 70, 70, 140, 280, 280, 700, 2200 and 2200 ppm for 20-80 weeks. Two groups were exposed 4 hr/day, 5 days/week at 2200 ppm for 20 or 80 weeks. The concentration x time (duration of exposure) values provided a series of theoretically equivalent exposure hazards.
An exposure-related increased incidence of liver, lung, Harderian gland and forestomach tumours and haemangiosarcomas and histiocytic sarcomas was reported with the overall LOEC apparently at 70 ppm (195 mg/m3).
Following statistical analyses, it was concluded that the product of isoprene concentration and length/duration of exposure was not a sufficient basis for predicting tumour risk. In addition, extrapolation of tumour probability between the high and low doses, based on cumulative exposure, was not appropriate or justified by the statistical models. It was concluded that, for this study, a threshold effect level and strong non-linearities with respect to concentration appeared to exist for tumour development.
Reference
The carcinogenic potential of isoprene was evaluated as a function of concentration, length of daily exposure, and weeks of exposure as independent variables. Exposure of mice to the varied concentrations and schedules did not produce any significant signs of general toxicity.
There was a concentration-related effect on survival due to increases in selected tumour development and associated mortality. Survival was near or below 50% after 95 weeks for mice exposed >280 ppm for 80 weeks - surviving mice in these groups were necropsied during week 96.
Isoprene exposure caused an increase in neoplasms of the lung, liver, Harderian gland, forestomach, lymphoreticular system of male mice and in the Harderian gland and pituitary gland of female mice at concentrations of 70 ppm and higher.
The product of concentration and length/duration of exposure was not a sufficient basis for prediction of tumour risk.
Table 2: Summary of isoprene exposure-related neoplasms in male mice
(based on Placke M, Griffis L, Bird M, Bus J, Persing R and Cox L Jr.1996, Toxicology, Vol. 113, pp. 253-262, Table 1)
Concentration (ppm) |
0 |
10 |
70 |
140 |
280 |
700 |
2200 |
|||||
Daily exposure (h) |
8 |
8 |
8 |
8 |
8 |
8 |
8 |
8 |
4 |
4 |
8 |
8 |
Weeks exposed |
80 |
80 |
40 |
80 |
40 |
20 |
80 |
80 |
20 |
80 |
40 |
80 |
Incidence of alveolar/bronchiolar adenomas and carcinomas |
||||||||||||
no tissues examined |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
49 |
50 |
adenoma |
11 |
16 |
8 |
4 |
10 |
16 |
13 |
23 |
14 |
15 |
29 |
30 |
carcinoma |
0 |
1 |
0 |
2 |
1* |
3* |
1* |
7* |
2* |
3* |
3* |
7* |
Incidence of hepatocellular adenomas and carcinomas |
||||||||||||
no tissues examined |
50 |
50 |
49 |
50 |
50 |
49 |
50 |
48 |
50 |
50 |
47 |
50 |
adenoma |
11 |
12 |
14 |
15 |
22 |
18 |
24 |
27 |
22 |
21 |
28 |
30 |
carcinoma |
9 |
6 |
11 |
9 |
10* |
12* |
16 |
17* |
12* |
15* |
18* |
16* |
Incidence of Harderian gland adenomas and carcinomas |
||||||||||||
no tissues examined |
47 |
49 |
48 |
50 |
50 |
49 |
50 |
49 |
49 |
50 |
50 |
50 |
adenoma |
4 |
4 |
13 |
9 |
12 |
16 |
17 |
26 |
19 |
28 |
31 |
35 |
carcinoma |
0 |
0 |
0 |
0 |
2 |
3 |
1 |
3 |
1 |
2 |
0 |
2 |
Incidence of heart haemangiosarcomas |
||||||||||||
no tissues examined |
49 |
50 |
49 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
49 |
50 |
haemangiosarcomas |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
1 |
4 |
1 |
1 |
1 |
Incidence of spleen haemangiosarcomas |
||||||||||||
no tissues examined |
49 |
48 |
47 |
50 |
50 |
47 |
50 |
48 |
48 |
50 |
47 |
49 |
haemangiosarcomas |
1 |
3 |
1 |
2 |
3 |
2 |
1 |
2 |
2 |
2 |
0 |
1 |
Incidence of forestomach squamous papillomas (SP) and squamous carcinomas (SC) |
||||||||||||
no tissues examined |
50 |
48 |
47 |
50 |
49 |
46 |
50 |
47 |
48 |
50 |
47 |
50 |
SP |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
2 |
1 |
SC |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
1 |
0 |
3 |
Incidence of histiocytic sarcomas |
||||||||||||
no tissues examined |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
histiocytic sarcoma |
0 |
2 |
2 |
2 |
1 |
8* |
4 |
2 |
5 |
7* |
7* |
2 |
Incidence of lymphomas |
||||||||||||
no tissues examined |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
lymphomas |
2 |
1 |
2 |
4 |
1 |
7 |
5 |
4 |
4 |
4 |
5 |
6 |
*incidences significantly greater than in control (p<0.05) |
Table 3: Summary of isoprene exposure-related neoplasms in female mice
(based on Placke M, Griffis L, Bird M, Bus J, Persing R and Cox L Jr.1996, Toxicology, Vol. 113, pp. 253-262, Table 2)
Concentration (ppm) |
0 |
10 |
70 |
Incidence of alveolar/bronchiolar adenomas and carcinomas |
|||
no tissues examined |
50 |
50 |
50 |
adenoma |
5 |
6 |
5 |
carcinoma |
0 |
0 |
0 |
Incidence of hepatocellular adenomas and carcinomas |
|||
no tissues examined |
50 |
50 |
50 |
adenoma |
4 |
6 |
3 |
carcinoma |
2 |
4 |
2 |
Incidence of Harderian gland adenomas and carcinomas |
|||
no tissues examined |
49 |
49 |
49 |
adenoma |
2 |
3 |
8* |
carcinoma |
0 |
0 |
0 |
Incidence of heart haemangiosarcomas |
|||
no tissues examined |
50 |
50 |
50 |
haemangiosarcomas |
0 |
0 |
0 |
Incidence of spleen haemangiosarcomas |
|||
no tissues examined |
50 |
49 |
50 |
haemangiosarcomas |
1 |
1 |
4 |
Incidence of forestomach squamous papillomas (SP) and squamous carcinomas (SC) |
|||
no tissues examined |
50 |
49 |
50 |
SP |
0 |
0 |
0 |
SC |
1 |
0 |
0 |
Incidence of pituitary adenoma |
|||
no tissues examined |
49 |
46 |
49 |
adenomas |
1 |
6 |
9* |
Incidence of histiocytic sarcoma |
|||
no tissues examined |
50 |
50 |
50 |
sarcomas |
4 |
5 |
6 |
Incidence of any lymphomas |
|||
no tissues examined |
50 |
50 |
50 |
lymphomas |
9 |
10 |
12 |
*incidences significantly greater than in control (p<0.05) |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 28 mg/m³
- Study duration:
- chronic
- Species:
- mouse
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Isoprene is classified as Cat 1B H350 'May cause cancer' and, since there is clear evidence of carcinogenicity of isoprene in mice but no data available to indicate carcinogenicity in humans, this position is unchanged based on review of the data.
Additional information
There are sufficient animal studies available on isoprene in order to assess for possible carcinogenic activity.
Isoprene has been examined for carcinogenic activity in both the mouse and rat.
Placke et al (1996) exposed groups of 50 male B6C3F1 mice to 0, 10, 70, 140, 280, 700, or 2200 ppm (equivalent to 0, 28, 195, 390, 780, 1950 or 6129 mg/m3) isoprene vapour by inhalation for 4 or 8 h/day, 5 days/week for 20, 40 or 80 weeks. Following exposure, animals were maintained without exposure to an intended termination time at 104 weeks. The combination of a range of doses and exposure times followed by a holding period and then termination at a standard time was undertaken to allow an investigation into the effect of integrated exposure x time in producing effects. Groups of 50 female B6C3F1 mice were also exposed to isoprene vapour at levels of 0, 10 or 70 ppm for 8 h/day for 80 weeks, and then held through to termination at 104 weeks.
There was a concentration-related effect on survival with approximately 50% or less of those animals exposed to concentrations of 280 ppm and higher surviving for 80 weeks. In male mice, isoprene exposure produced an increase in histiocytic sarcomas and in neoplasms of the liver, lung, Harderian gland and forestomach. The incidence of hepatocellular adenomas and carcinomas was increased as were haemangiosarcomas and histiocytic sarcomas of the liver. Primary alveolar/bronchiolar adenomas and carcinomas were significantly increased. The incidence of Harderian gland adenomas was significantly increased. Harderian gland carcinomas were not as numerous as adenomas but were present in the higher concentration groups. Neoplasms in the stomach included squamous cell carcinomas of the stomach. Exposed mice also had a slight increase in the incidence of haemangiosarcomas in the spleen and heart compared to controls. In female mice, which were only exposed to lower levels of isoprene, increases were observed in haemangiosarcomas in the spleen, Harderian gland adenomas and adenomas of the pituitary gland. No increased in tumours were seen at 10 ppm in either male or female mice.
Melnick et al (1994) exposed male Fischer F344 rats and male B6C3F1 mice to 0, 70, 220, 700, 2200, or 7000 ppm (equivalent to 0, 195, 613, 1950, 6129 or 19503 mg/m3) isoprene vapour by inhalation for 6h/day, 5 days/week for 26 weeks. After exposure, 10 animals per group were killed and examined, with the remaining 30 animals per group continuing without exposure for a further 26 weeks before termination.
In mice, incidences of malignant lesions in the liver, lung, forestomach, and Harderian gland were significantly increased following both the 26 week exposure and 26 week recovery periods at doses of 700 ppm and above. There was no clear dose response seen with most tumours and the carcinogenic effects of isoprene produced at 700 or 2200 ppm were not much different from those at 7000 ppm. The survival was reduced in the 7000 ppm group with early deaths attributed to various neoplastic lesions and terminations due to hindlimb paralysis.
In rats, interstitial cell hyperplasia of the testis was observed after 26 weeks of exposure to 7000 ppm isoprene. Following the 26-week recovery period, the only effect reported was a marginal increase in benign testicular interstitial cell tumours in the 7000 ppm group.
The NTP exposed groups of male and female F344/N rats to 220, 700, or 7000 ppm (equivalent to 613, 1950, 19503 mg/m3) isoprene by inhalation, 6/ day, 5 days/week, for 105 weeks (NTP 1999).
Isoprene exposures were associated with increases in rates of benign tumours in the testes and kidney of males, and in the mammary gland of male and females. No significant increases were seen for malignant tumours in this study. Several rare neoplasms were observed in the brain of exposed female rats. However, the fact that they were from different cell types makes it difficult to conclude that they are treatment related.
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