Isooctyl 3-mercaptopropionate

Endpoint summary

Description of key information

IOMP is harmful via the oral route. IOMP is non-toxic via dermal and inhalation route.

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:

16 Sept 1998 - 20 Oct 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Department of health of the government of the United Kingdom

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: males: 201 - 232 g; females: 200 - 218 g
- Fasting period before study: overnight fast
- Housing: Animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum): free access to food (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK)
- Water (ad libitum): free access to mains drinking water
- Acclimation period: minimum acclimation period of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): relative 43 - 70
- Air changes (per hr): approximately 15 x / hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 35.4, 50.0 or 70.7 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Arachis oil was used because the test material did not dissolve in distilled water.

Doses:

Males: 354, 500 and 707 mg/kg bw
Females: 354 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: ½, 1, 2, 4 hours after dosing and subsequently once daily for 14 days
- Frequency of observations and weighing: once daily, body weight was recorded on day 0 and on days 7 and 14 or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Using the mortality data obtained, the acute oral median lethal dose (LD50) and 95 % confidence limits of the test material were calculated using a probit method of Finney D.J. ´Probit Analysis´1971, Cambridge University Press. The LD50 and 95 % confidence limits were calculated for males only.

Preliminary study:

The male treated with 500 mg/kg bw was found dead four hours after dosing. Clinical signs of toxicity noted in the animal treated with 500 mg/kg bw were hunched posture, lethargy, decreased respiratory rate, labored respiration, ataxia, occasional body tremors, pilo-erection and ptosis. The female treated with 500 mg/kg bw recovered four days after dosing. Hunched posture was noted in animals treated with 50 mg/kg during the day of dosing and up to one day after dosing.
Based on this information, dose levels of 707, 500 and 354 mg/kg body weight were selected for the main study.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

674 mg/kg bw

95% CL:

> 454 - <= 1 000

Mortality:

Deaths were noted at dose levels of 707 (3 males found dead approximately 3 hours after dosing) and 500 mg/kg (1 male 2 hours after dosing) bw during the day of dosing (Table 1).

Clinical signs:

other: Common signs of systemic toxicity noted in all dose groups were hunched posture, lethargy, decreased respiratory rate and labored respiration. Ataxia was commonly noted in animals treated with 707 and 500 mg/kg bw. Common signs of systemic toxicity noted

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were hemorrhagic or abnormally red lungs, dark liver and dark kidneys. No abnormal findings were observed at necropsy of animals that were killed at the end of the study.

Other findings:

Female animals were considered not to be markedly more sensitive to the test material than male animals.

Table 1. Acute oral toxicity of IOMP
Dose [mg/kg bw]	Toxicological results*	Time of death	Mortality (%)
Males
354	0/5/5	–	0
500	1/5/5	1 h	20
707	3/5/5	4 h	60
LD50= 674 mg/kg bw
Females
354	0/5/5	–	0

* first number = number of dead animals

  second number = number of animals with signs of toxicity

  third number = number of animals used

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 = 674 mg/kg bw

Executive summary:

In a study according to OECD TG 401, male and female Sprague-Dawley rats (5/sex/dose) were administered a single dose of iOMP at dose levels of 354, 500 and 707 mg/kg bw (males) or 354 mg/kg bw (females). The animals were observed for 14 days.

Deaths were noted at dose levels of 707 (3 males found dead approximately 3 hours after dosing) and 500 mg/kg (1 male 2 hours after dosing) bw during the day of dosing.

Common signs of systemic toxicity noted in all dose groups were hunched posture, lethargy, decreased respiratory rate and labored respiration. Ataxia was commonly noted in animals treated with 707 and 500 mg/kg bw. Common signs of systemic toxicity noted in animals treated with 707 mg/kg bw were prostration, clonic and tonic convulsions. Occasional body tremors were commonly noted in females treated with 354 mg/kg bw with incidents of occasional body tremors noted in animals treated with 707 and 500 mg/kg bw. Incidents of vocalization and chromodacryorrhoea were noted in animals treated with 707 mg/kg bw with incidents of prostration, increased salivation and ptosis and an isolated incident of pilo-erection noted in animals treated with 500 mg/kg bw. Incidents of splayed gait were noted in animals treated with 500 and 354 mg/kg bw with incidents of ataxia noted in males treated with 354 mg/kg.

Surviving animals recovered four to eight days after dosing.

The LD50 (males) was 674 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

674 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

11 Sep 2008 - 26 Nov 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: First addendum to OECD Guidelines for Testing of Chemicals, Section 4, No. 404, "Acute Dermal Irritation/Corrosion" adopted 24th April, 2002.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Arbeitsschutz, Arbeitsmedizin und Sicherheitstechnik

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 190 - 200 g
- Housing: Semi-barrier condition in an air conditioned room; animals were kept in IVC cages, type III H, polysulphone cages on Altromin saw fiber bedding
- Diet (ad libitum): free access to Altromin 1324 maintenance diet for rats and mice
- Water (ad libitum): free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, micro biologically controlled at frequent intervals)
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): artificial light, sequences being 12 hours light, 12 hours dark

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: no less than 10 %
- Type of wrap if used: The test article was held in contact with the skin by a dressing which consisted of a gauze-dressing and non-irritating tape, and was fixed with an additional dressing in a suitable manner.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure, residual test item was removed by using aqua ad injectionem (B. Braun Melsungen; Lot 7494A191).
- Time after start of exposure: The test article was held in contact with the skin throughout a 24 hour period.


TEST MATERIAL
- Amount(s) applied (weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

A total of five animals was made up of one animal from the sighting study dosed at the selected dose level together with additional four animals.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made immediately after the dosing, at least once during the first 30 minutes, periodically during the first 24 hours, with special attention given during the first 4 hours, and daily thereafter. Primary skin irritation was assessed 1, 2 and 3 days after removal of the test substance.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Primary skin irritation was assessed using the scoring system laid down in OECD 404.

Preliminary study:

A sighting study was performed to allow the selection of the appropriate starting dose for the main study. The test article was applied to one female at a dose of 2000 mg/kg body weight (oral LD50 rat >2000 mg/kg bw).
As the animal survived, the main test was performed with the same dose, with four additional animals.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured.

Clinical signs:

other: In the main study 1 out of 4 animals showed a bloody nose on day 9 after the application of the test item. This finding is considered to be incidental and not treatment related. No other clinical signs of toxicity were observed throughout the observation

Body weight:

other body weight observations

Remarks:

For animal no. 3, a minimal weight loss of 1 g during the first week was recorded. The body weight development of further animals was within the expected range.

Gross pathology:

At necropsy of the main study, 1 out of 4 animals showed a clearly visible prominence and light-colored deposits on the spleen as well as dark-colored spots on the right heart ventricle. In the absence of clinical signs, this isolated finding does not appear to be of toxicological significance or a resultof treatment. Except for acute injection of blood vessels in the abdominal region, which was caused by the euthanasia injection, no specific gross pathological changes were found in any of the other animals.

Other findings:

No signs of skin irritaion were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 was determined to be > 2000 mg/kg bw. Therefore, the test item Isooctyl mercaptopropionate is unclassified according to the criteria of Annex VI to Commission Directive 2001/59/EC. Judging from the absence of local skin effects after 24 hours of exposure to 2000 mg/kg bw, it is concluded that the test article is not a primary skin irritant.

Executive summary:

This study was conducted to assess the acute dermal toxicity of the test item iOMP after a single dermal administration to 5 female Wistar rats in accordance eith OECD TG 434.

The test item was applied as a single dose uniformly over an area which was approx. 10% of the total body surface.
The test item was held in contact with the skin by a dressing which consisted of a gauze-dressing and non-irritating tape, and was fixed with an additional dressing in a suitable manner. The starting dose was 2000 mg/kg body weight.

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure, residual test item was removed by using aqua ad injectionem.

The dermal LD50 was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

In a study according to OECD TG 401, male and female Sprague-Dawley rats (5/sex/dose) were administered a single dose of iOMP at dose levels of 354, 500 and 707 mg/kg bw (males) or 354 mg/kg bw (females). The animals were observed for 14 days.

Deaths were noted at dose levels of 707 (3 males found dead approximately 3 hours after dosing) and 500 mg/kg (1 male 2 hours after dosing) bw during the day of dosing.

Common signs of systemic toxicity noted in all dose groups were hunched posture, lethargy, decreased respiratory rate and labored respiration. Ataxia was commonly noted in animals treated with 707 and 500 mg/kg bw. Common signs of systemic toxicity noted in animals treated with 707 mg/kg bw were prostration, clonic and tonic convulsions. Occasional body tremors were commonly noted in females treated with 354 mg/kg bw with incidents of occasional body tremors noted in animals treated with 707 and 500 mg/kg bw. Incidents of vocalization and chromodacryorrhoea were noted in animals treated with 707 mg/kg bw with incidents of prostration, increased salivation and ptosis and an isolated incident of pilo-erection noted in animals treated with 500 mg/kg bw. Incidents of splayed gait were noted in animals treated with 500 and 354 mg/kg bw with incidents of ataxia noted in males treated with 354 mg/kg.

Surviving animals recovered four to eight days after dosing.

The LD50 (males) was 674 mg/kg bw.

 

Acute dermal toxicity

This study was conducted to assess the acute dermal toxicity of the test item iOMP after a single dermal administration to 5 female Wistar rats in accordance eith OECD TG 434.

The test item was applied as a single dose uniformly over an area which was approx. 10% of the total body surface.
The test item was held in contact with the skin by a dressing which consisted of a gauze-dressing and non-irritating tape, and was fixed with an additional dressing in a suitable manner. The starting dose was 2000 mg/kg body weight.

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure, residual test item was removed by using aqua ad injectionem.

The dermal LD50 was determined to be > 2000 mg/kg bw.

Justification for classification or non-classification

The oral LD50 of 674 mg/kg leads to the following classification:

GHS: Acute Tox. 4, H302. Harmful if swallowed.

No classification is warranted for dermal route.