Captan

Endpoint summary

Description of key information

1. Acute (one single dose) study oral (gavage), rat m/f, (OECD 401 (1987) = EEC B.1 (1992): LD50 > 2000 mg/kg bodyweight.

2. Acute (single 4 hour exposure) study inhalation, rat m/f, EEC B.2 (1984), OECD 403 (1984): LC50 = 0.67 mg/l (female, 95% confidence limits 0.36 - 1.22).
In accordance with the provisions of regulation 1272/2008, Annex I, 3. is classified as acute toxic cat. 3 .

3. Acute (one single application) study dermal, rabbit m/f, EPA FIFRA, Subdivision F, §81-2 (1981) = EEC B.3 (1992): LD50 > 2000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 July 1991 to 30 August 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1984

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Batch no.: 4102
- Date received: 9 July 1991
- Description: white powder
- Storage conditions: room temperature

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were housed In groups of five by sex in solid-floor polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Mitham, Essex, U.K.) was allowed throughout the study. The animal room was maintained at a temperature of 20 - 23°C and relative humidity of 48 - 61%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

For the purpose of the study the test material was freshly prepared, as required, as a suspension at the appropriate concentration in distllled water. All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume adminlstered to each animal was calculated according to Its fasted bodywelght at the time of dosing.

Doses:

A group of ten rats (five males and five females) was dosed as follows: 2000 mg/kg (Dose Level), 200 mg/ml (Concentration), 10 ml/kg (Dose Volume)

No. of animals per sex per dose:

One group of five male and five female rats, 10 animals/dose

Control animals:

no

Details on study design:

RANGE-FINDING STUDY: A range-finding study was performed to establish a dosing reglme as follows:A group of two rats (one male and one female) was dosed as follows: 2000 mg/kg (Dose Level), 200 mg/ml (Concentration), 10 ml/kg (Dose Volume).Deaths and overt signs of toxicity were recorded 1, 2 and 4 hours after dosing and then dally for five days. Indlvidual bodywelghts were recorded on the day of dosing to allow calculatlon of indlvidual treatment volumes. No necropsles were performed. All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume adminlstered to each animal was calculated according to Its fasted bodywelght at the time of dosing.
MAIN STUDY: Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14. At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological exaralnation. This conslsted of an external examination and opening of the abdominal and thoracic cavities, The appearance of any macroscopic abnormalities was recorded. No tissues were retalned.
EVALUATION OF DATA: Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.Using the mortality data obtained, an estlmate of the acute oral medlan lethal dose (LD50) of the test material was made.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of captan in rat is greater than 2000 mg/kg bw in both males and females. In accordance with the provisions of regulation 1272/2008, Annex I, 3.1, it is proposed classification is not required.

Executive summary:

The study was performed to assess the acute oral toxicity of captan in the Sprague-Dawley strain rat. The method used followed OECD Guidelines No. 401 "Acute Oral Toxicity" referenced as Method B1 in the regulation 440/2008. Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a suspension in distilled water at a dose level of 2000 mg/kg bodyweight.

The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be higher than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 July 1991 to 5 September 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Batch no.: 4102
- Date received: 9 July 1991
- Description: white powder
- Storage conditions: room temperature

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- groups of fifteen male and fifteen female fasted Sprague-Dawley strain rats
- Source: Charles River (UK) Ltd., Manston, Kent
- weight: males: 226 - 303g, females: 206 - 233g
- age: eight to ten weeks
- free access to mains drinking water and food
- room temperature: 20 - 23°C
- relative humidity: 47 - 61%.

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 1.6 - <= 1.8 µm

Geometric standard deviation (GSD):

>= 0.46 - <= 0.52

Details on inhalation exposure:

Atmosphere Generation: A dust atmosphere was produced from the test material using a 'Wright Dust Feed' mechanism located at the top of the exposure chamber and driven by a variable speed motor. The dust feed was connected to a metered compressed air supply. A particle separator was introduced before the aerosol entered the exposure chamber in order to remove large particles. Compressed air was supplied by means of a Gast 2HBB-10-P25Y oil free compressor and was passed through a water trap and respiratory quality filters which removed particulate material above 0.005 µm before it was introduced to the dust feed. The cylindrical exposure chamber has a volume of approximately 30 litres. The concentration within the exposure chamber was controlled by adjusting the rate of the motor and the air flow rate through the chamber. The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure. Homogeneity of the test atmosphere within the chamber was not specifically determined during this study, but, chambers of the same design have been fully validated and shown to produce evenly distributed atmospheres in the animals' breathing zone with a wide variety of test materials. Prior to the start of the study test material atmospheres were generated within the exposure chamber. During these periods air flow settings, test material input and the sampling system was varied to achieve the required atmospheric concentrations. Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring. Only the noses of the animals were exposed to the test atmosphere. Three groups, each of ten rats (five males and five females) were subjected to a single exposure to the test material for a period of up to four hours. Based on the expected toxicity of the test material, a target concentration of 5.0 mg/litre was used for the first exposure. Further concentrations were selected after consideration of the results of the previous exposure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The actual concentration of the test material was measured at least every 15 minutes during each exposure period.

Duration of exposure:

4 h

Concentrations:

nominal concentrations: 0.4, 1.8 and 12.6 mg/L captan

No. of animals per sex per dose:

three groups of five male and five female rats, 10 animals/dose

Control animals:

no

Details on study design:

Captan technical was administered as a single four-hour exposure (nose only) to Sprague-Dawley strain rats. Three groups of five males and five females were each exposed to nominal concentrations of 0.4, 1.8 and 12.6 mg/L captan. Test atmospheres were generated by the suspension of captan particulate in air using a Wright dust feed generator. The air flow rate was 22 L/min, providing 44 air changes/minute. Animals were observed for mortality and clinical signs at hourly intervals during exposure, for one hour after exposure and then daily until 14 days after exposure. Body weight was recorded on the day of exposure and then seven and 14 days after exposure. Rats were necropsied and observed for gross pathological changes at the end of the observation period.

Statistics:

Using the mortality data obtained, the acute inhalation median lethal concentration (LC50) and 95% confidence limits of the test material were calculated using the method of Thompson W.R., Bact. Reviews, 11, 115 - 145 (1947). The LC50 and 95% confidence limits were calculated for males and females separately. Clinical observations, bodyweight and necropsy data were examined for any adverse effects resulting from treatment.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.78 mg/L air

Based on:

test mat.

95% CL:

>= 0.49 - <= 1.23

Exp. duration:

4 h

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

0.9 mg/L air

Based on:

test mat.

95% CL:

>= 0.43 - <= 1.9

Exp. duration:

4 h

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

0.67 mg/L air

Based on:

test mat.

95% CL:

>= 0.36 - <= 1.22

Exp. duration:

4 h

Mortality:

All animals exposed to 4.81 mg/L died or were killed in extremis. Three of the males killed in extremis upon removal from the chamber showed gasping respiration and wer comatose. One male and one female from the 0.94 mg/L treatment group were killed in extremis shortly after removal from the treatment chamber.

Clinical signs:

other: During exposure animals were observed to have wet fur and a decreased respiratory rate. Upon removal from the test chamber common signs of toxicity were hunched posture, lethargy, pilo-erection, ataxia and ptosis. Incidences of gasping, laboured and noisy

Body weight:

During the first week after exposure, one female from the 0.94 mg/L group showed normal body weight gain and two showed body weight loss. Normal weight gain was resumed during week two. Body weight gain in all animals from the 0.23 mg/L group was normal.

Gross pathology:

Animals that died or were killed in extremis showed common abnormalities including lungs that appeared haemorrhagic, swollen and fluid filled. An incident of pale lungs and patchy pallor of the liver and reddening or congestion of the small intestine was also noted in animals exposed to 4.81 mg/L. Additional observations in two animals in the 0.94 mg/L group that died were signs of fluid in the nasal and/or oral tract, fluid in the lung cavity, dark liver and haemorrhage, reddening or congestion of the small intestine.

Table 7.2.2-02 Acute inhalation toxicity of captan in rats: summary of toxicity

 

Concentration		Toxicological results^2	Duration of signs^2	Time of death^3	LC50 mg/L (14 days)
Nominal	Achieved^1
male
0.4	0.23 ± 0.04	0/5/5	during exposure - 5 d^4	-	0.90 (0.43 - 1.90)
1.8	0.94 ± 0.05	3/5/5	during exposure - 7 d^4	during exposure^5-1h^4
12.6	4.81 ± 0.36	5/5/5	during exposure	during exposure^5
female
0.4	23 ± 0.04	0/5/5	during exposure - 4 d^4	-	0.67 (0.36 - 1.22)
1.8	0.94 ± 0.05	4/5/5	during exposure - 7 d^4	1 h - 2 d^4
12.6	4.81 ± 0.36	5/5/5	during exposure	during exposure^5

¹Mean ± sd.

²Number of animals which died/number of animals with clinical signs/number of animals in dose group.

³Day number of test.

⁴Post-exposure.

⁵Deaths occurred during exposure or immediately following removal from test chamber at 4 hours.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute (4-hour) inhalation LC50 for captan in rats was 0.90 mg/L and 0.67 mg/L in males and females, respectively. The combined sex LC50 was 0.78 mg/L (95% confidence limits 0.49 - 1.23). In accordance with the provisions of regulation 1272/2008, Annex I, 3.1 captan is classified as acute toxic cat. 3 (H331).

Executive summary:

A study was performed to assess the acute Inhalation toxicity of the test material, as supplied, by exposing groups of ten Sprague-Dawley strain rats (five males and five females) to various concentrations of a dust atmosphere. The animals were exposed for up to four hours using a nose only exposure system.

The method applied was according to OECD Guidelines No. 403 (1981)

"Acute Inhalation Toxicity" referenced as method B.2./14 in the Regulation (EC) No 440/2008. The test system was chosen because the rat has been shown to be a suitable model for this type of study and is recommended in the test method.

Clinical Observations:

During exposure signs of wet fur and decreased respiratory rate were noted. On removal from the chamber common signs of toxicity noted were hunched posture, lethargy, pllo-erection, ataxia and ptosis. Incidents of gasping, laboured and noisy respiration and red/brown stains around the snout were apparent. Isolated Incidents of pallor of the extremities, dehydration and frequent sneezing were also noted. Surviving animals treated with 0.94 mg/litre appeared normal on day seven and those treated with 0.23 mg/litre appeared normal four to five days following exposure

Bodyweight:

During week one following exposure to 0.94 mg/litre one surviving animal showed normal bodyweight gain and two showed bodyweight loss. Normal bodyweight gain was noted during week two. Expected bodyweight gain was noted in all animals exposed to 0.23 mg/litre throughout the study.

Necropsy:

Common abnormalities noted at necropsy were haemorrhage and swollen appearance of the lungs and presence of fluid in the lungs. All animals exposed to 4,81 mg/litre and two exposed to 0.94 mg/litre showed reddened or congested small intestines. There were two incidents of fluid present in the nasal/oral tract in animals exposed to 0.94 mg/litre.

Isolated incidents of pale lungs, fluid present in the lung cavity, patchy pallor of the liver, dark liver and haemorrhage in the small Intestine were also noted. Three surviving animals exposed to 0.94 mg/litre and all animals exposed to 0.23 mg/litre showed no abnormalities.

The acute inhalation median lethal concentration (LC50) and 9S% confidence limits of the test material CAPTAN TECHNICAL, in the Sprague-Dawley strain rat, were calculated to be:

All animals: 0.78 (0.49 - 1.23) mg/litre

Males only: 0.90 (0.43 - 1.90) mg/litre

Females only: 0.67 (0.36 - 1.22) mg/litre

In consquence captan has to be classified as acute toxic cat. 3 (H331) according to Eu regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

670 mg/m³ air

Physical form:

inhalation: dust

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 February 1984 to 3 March 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Physical state: white powder
- Purity: 90.5 %
- Batch number: WRC 4921-26-12
- Date of arrival: 13 February 1984

Species:

rabbit

Strain:

other: Stauffland albino rabbits

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

three days

Doses:

dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 animals/f/m per dose

Control animals:

yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Clinical signs:

other:

Clinical findings: There were no mortalities. All animals appeared normal throughout the observation period, except two rabbits which had wet areas around the eyes on days 4 and 5.

Local findings: There were no signs of dermal irritation.

Autopsy: No abnormalities were observed at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information In accordance with the provisions of regulation 1272/2008, Annex I, 3.1 classification is not required Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 of captan in rabbits was higher than 2000 mg/kg bw in males and females. In accordance with regulation 1272/2008, Annex I, 3.1 classification is not required

Executive summary:

A single dose of captan was applied to the closely clipped abdominal skin of male and female Stauffland albino rabbits at a dose of 2000 mg/kg bw (5 animals/sex). The skin was abraded on half of the animals and left intact on the others. The area was covered with a protective binder. The binder and test material was removed after 24 hours, the area inspected and rewrapped in a gauze binder. After three days, the gauze binder was removed. A concurrent control (2 animals/sex) was also conducted. All animals were observed for clinical signs for at least 14 days after treatment and were necropsied at the end of the observation period.

Clinical findings: There were no mortalities. All animals appeared normal throughout the observation period, except two rabbits which had wet areas around the eyes on days 4 and 5.

Local findings: There were no signs of dermal irritation.

Autopsy: No abnormalities were observed at necropsy.

Captan was in this study of low toxicity via dermal route of exposure.

Based on this study captan is not classified to be acute toxic for dermal exposure. Nevertheless positive results for sensitisation (Dreher, D.M. 1991) have to be considered leading to classification as skin sensitizing cat. 1 (H317).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

For oral application of 2000 mg/kg bw captan to rats no mortalities were observed. All animals showed expected gain in bodyweight during the study but no abnormalities were noted at necropsy.

For inhalation exposure with captan all animals treated showed clinical signs during exposure (e.g. wet fur, decreased respiratory rate) and after exposure (e.g. hunched posture, lethargy, pilo-erection, ataxia, ptosis). LC 50 value was determined 0.67 mg/l. Due to inhalation toxicity captan has to be classified as acute toxic for inhalation cat. 3.

For dermal application of 2000 mg/kg bw captan to albino rabbits no mortalities were noted. All animals appeared normal throughout the observation period, except two rabbits which had wet areas around the eyes on days 4 and 5. There were no signs of dermal irritation and no abnormalities were observed at necropsy.

Justification for classification or non-classification

According to EU regulation 1272/2008 captan is neither toxic for dermal nor for oral exposure as classification thresholds (Annex I, chapter 3.1) were not reached. For inhalation exposure an LC50 value of 670 mg/m3 was determined, leading to classification as acute toxic category 3 by inhalation.