Captan

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Captan

EC Number:

205-087-0

EC Name:

Captan

Cas Number:

133-06-2

Molecular formula:

C9H8Cl3NO2S

IUPAC Name:

2-[(trichloromethyl)sulfanyl]-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

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

Test animals

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%.

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

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

Effect levels 2

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

Effect levels 3

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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.