Isooctyl 3-mercaptopropionate

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Isooctyl 3-mercaptopropionate

EC Number:

250-157-6

EC Name:

Isooctyl 3-mercaptopropionate

Cas Number:

30374-01-7

Molecular formula:

C11H22O2S

IUPAC Name:

2-methylheptyl 3-sulfanylpropanoate

Details on test material:

- Name of test material (as cited in study report): Iso-octyl 3-mercaptopropionate
- Analytical purity: 99.6% w/w
- Purity test date: 1996-10-01
- Lot/batch No.: B98E2688
- Physical state: colourless liquid
- Storage condition of test material: room temperature in the dark

Test animals

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

Administration / exposure

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.

Results and discussion

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.

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.