Reaction mass of 2-hydroxy-4-(methylthio)butanoic acid and 2-hydroxy-4-(methylthio)butanoic acid dimer

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 25 June to 20 September 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted similarly to OECD Guideline 402 with minor deviations: no certificate of analysis, occlusive conditions were used

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

no certificate of analysis, occlusive conditions were used

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-4-(methylthio)butyric acid

EC Number:

209-523-0

EC Name:

2-hydroxy-4-(methylthio)butyric acid

Cas Number:

583-91-5

Molecular formula:

C5H10O3S

IUPAC Name:

2-hydroxy-4-(methylthio)butanoic acid

Details on test material:

- Name of test material (as cited in study report): Alimet
- Source: Monsanto Company
- Physical state: Amber liquid
- Lot/batch No.: CBA 0506 AL2/NBP 2334433
- Storage condition of test material: Room temperature
- Density: 1.2322 g/mL

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland Laboratory Animals, Denver, USA
- Age at study initiation: Young adults (at least 8 weeks old); females were nulliparous and non-pregnant
- Weight at study initiation: Males: 2.3-3.0 kg; females: 2.4-2.9 kg
- Housing: Individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina #5326), ad libitum
- Water (e.g. ad libitum): Municipal water supply, ad libitum
- Acclimation period: 24-31 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-70 °F
- Humidity (%): 30-70%
- Photoperiod (h dark / h light): 12 h dark / 12 h light

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: 10% of body surface area
- Type of wrap if used: Test material applied directly, covered by gauze and then wrapped with an impervious plastic sleeve

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were not washed but wiped free of excess test material
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume with unit): 1.6 or 4.1 mL/kg in 2000 or 5000 mg/kg bw groups, respectively

Duration of exposure:

24 hours

Doses:

2000 and 5000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed twice daily for viability check; pharmacological/toxicological signs were observed at 1, 2 and 4 hours after dosing and daily thereafter for 14 days; weighed at pre-test (at the time of clipping), pre-dose, Day 7 and Day 14
- Necropsy of survivors performed: Yes; surviving animals were killed by intravenous overdose of sodium pentobarbital and examined grossly

Statistics:

No data

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- At 2000 mg/kg bw: 0/5 male and 0/5 female died
- At 5000 mg/kg bw: 4/5 males and 1/5 female died

Clinical signs:

other: - Nasal discharge and/or reddening of the eye were observed in one animal in each group on the day of dosing - Severe abnormalities (hypothermia, prostration, decreased food consumption, hypoactivity, hypopnea and ocular discharge) were observed in anima

Gross pathology:

- Necropsy of the dead animals revealed abnormalities like postmortem autolytic changes (discolorations) or antemortem stress (testes in body cavity, gastrointestinal irritation)
- Necropsy of the surviving animals revealed reddening of the stomach walls

Other findings:

- Local irritation reactions at application site: Most animals exhibited severe dermal effects (necrosis followed by eschar formation, fissuring and/or exfoliation of the eschar tissue), generally affecting less than 25% of the dose site, which persisted throughout the study

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal combined LD50 for Alimet is higher than 2000 mg/kg bw in rabbits and therefore it is not classified according to the criteria of the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In an acute dermal toxicity study performed similarly to OECD guideline 402, groups of New Zealand White rabbits (5/sex/dose) received a single dermal dose of Alimet at 2000 and 5000 mg/kg bw at dose volume of 1.6 or 4.1 mL/kg, respectively on clipped area of the trunk representing 10% of the total body surface area. The application was occluded and exposure was for 24 hours. Parameters evaluated included survival, clinical observations, body weight gain and necropsy findings in all animals after a 14 days observation period.

Mortality was 0/5 male and 0/5 female at 2000 mg/kg bw and 4/5 males and 1/5 female at 5000 mg/kg bw. All animals exhibited little or no weight change, although one female in 5000 mg/kg bw exhibited loss of weight on Day 7. Clinical signs noted in several animals were nasal discharge and/or reddening of the eye. Severe abnormalities (hypothermia, prostration, food consumption decrease, hypoactivity, hypopnea and ocular discharge) were observed in animals which died on Day 2 or 3. Necropsy of the dead animals revealed abnormalities like postmortem autolytic changes (discolorations) or antemortem stress (testes in body cavity, gastrointestinal irritation). Necropsy of the surviving animals revealed reddening of the stomach walls. The acute dermal combined LD50 was greater than 2000 mg/kg bw.

 

Adverse dermal reactions noted were severe dermal effects (necrosis followed by eschar formation, fissuring and/or exfoliation of the eschar tissue), generally affecting less than 25% of the dose site, which persisted throughout the study.

 

Under the test conditions, Alimet is not classified according to the criteria of the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).