m-toluic acid

Endpoint summary

Description of key information

LD50 (oral, male and females rats) > 2000 mg/kg bw, no clinical signs of systemic toxicity were observed throughout the 14 -day observation period.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

no

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: sealed at a cool (4 °C) and dark place
- Stability under test conditions: stable during use period
- Solubility and stability of the test substance in the solvent/vehicle: uniform administration solution in 1 % methylcellulose in water


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: dissolved in 1 % methylcellulose in water

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 5 weeks
- Weight at study initiation:
males:
mean body weight at time of administration: 134 g (range: 127 - 138 g)
females:
mean body weight at time of administration: 116 g (range: 110 - 120 g)
- Fasting period before study: approximately 12.5 hours
- Housing: in stainless steel wire mesh cages, separated by sex
acclimation period: three rats were co-housed,
after administration: two to three rats were co-housed
- Diet ad libitum: obtained from Nosan Kako Co., Ltd., Japan, national type feed laboratory MR stock, Lot No. 97.12.61 (assumed)
- Water ad libitum: sterile tap water irradiated with ultraviolet rays
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22 °C
- Humidity (%): 52 - 59 %
- Air changes (per hr): 10 times or more per hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

1 % in aqueous solution

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1 mL/kg bw

Doses:

0, 1000 and 2000 mg/kg

No. of animals per sex per dose:

5 males/ 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations were carried out 1, 3 and 6 hours after administration and daily thereafter until day 14.
Weighing was carried out shortly before administration and on days 1,3,7 and 14 after administration
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights

Statistics:

The LD50 could not be calculated because no lethality occurred.

Preliminary study:

3 males and 3 females per group were exposed to doses of 1000, 2000 and 4000 mg/ kg bw. One male of the 4000 mg/ kg bw dose group displayed weak acute toxicity.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

no effects observed

Body weight:

no effects observed

Gross pathology:

no effects observed

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (male and females rats) > 2000 mg/kg bw
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

A high quality study report, also assessed for the high production volume (HPV) program in order to prepare dossiers of screening information data sets (SIDS), was evaluated.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987-02-24

Deviations:

yes

Remarks:

one sex only; one dose only instead of 3 doses; observation period lasted 7 d instead of 14 d; clinical signs were not reported (exception: skin reaction); gross pathology & body weight measurements were missing; housing conditions incompletely described

GLP compliance:

not specified

Remarks:

not specified in the study report

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was finely pulverized in an agate mortar

Species:

rabbit

Strain:

other: Japanese white Kbs:JW

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kitayama Labes Co., Ltd.
- Weight at study initiation: 2.1 - 2.5 kg
- Diet (ad libitum): solid feed RC-4 (obtained from Oriental Yeast K.K)
- Water (ad libitum): tap water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 2 °C
- Humidity: 55 ± 6 %

Type of coverage:

occlusive

Vehicle:

other: distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: on the day before the test, the hair on the back of the rabbits was removed with an electric clipper. The test item was applied within a circle of 3 cm. The test item was applied onto intact and abraded skin of each rabbit.
- Type of wrap if used: two layers of gauze patch fixed with Tegaderm (3M) and Ju Picot 5 (obtained from Tokyo Material Research Institute) were used to cover the area of exposure after test item application.

REMOVAL OF TEST SUBSTANCE
- Washing: the application site was cleaned with a gauze soaked in water after application.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1000 mg/animal (0.5 g test substance/intact skin area and 0.5 g test substance /abraded skin)

Duration of exposure:

24 hours

Doses:

1000 mg/animal (0.5 g test substance/intact skin area and 0.5 g test substance /abraded skin)

No. of animals per sex per dose:

6 male rabbits

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: 24, 48, 72 and 168 hours
The extent of erythema and oedema of the skin was evaluated according to the Draize scale.

Statistics:

not applicable

Sex:

male

Based on:

test mat.

Remarks on result:

other: see "Remarks"

Remarks:

After a test item application, all animals survived until the end of the observation period. Following the 24 hour exposure, three animals of the 6 treated animals (intact skin of one animal and abraded skin of two animals) displayed a mild erythema (grade 1) at the 24 hour observation (disappeared after 48 h). No further signs of erythema and/or oedema were observed during the observation period.

Mortality:

All animals survived until the end of the observation period.

Clinical signs:

Following the 24 hour exposure, three animals of the 6 treated animals (intact skin of one animal and abraded skin of two animals) displayed a mild erythema (grade 1) at the 24 hour observation (disappeared after 48 h). No further signs of erythema and/or oedema were observed during the observation period.

Body weight:

no data

Gross pathology:

no data

Interpretation of results:

study cannot be used for classification

Conclusions:

After a test item application of 1000 mg/animal (0.5 g test substance/intact skin area and 0.5 g test substance /abraded skin), all animals survived until the end of the observation period. Following the 24 hour exposure, three animals of the 6 treated animals (intact skin of one animal and abraded skin of two animals) displayed a mild erythema (grade 1) at the 24 hour observation (disappeared after 48 h). No further signs of erythema and/or oedema were observed during the observation period.

Reference 2

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Sufficient evidence available.

Justification for classification or non-classification

LD50 (oral, male and females rats) > 2000 mg/kg bw

Sufficient evidence available, m-toluic acid is considered non toxic via the dermal route of exposure.

According to the Regulation (EC) No 1272/2008 and its subsequent amendments and corrections, m-toluic acid does not have to be classified and has no obligatory labelling requirement for acute oral and dermal toxicity. m-Toluic acid is not classified for acute inhalative toxicity because of lacking data.