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Administrative data

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:
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 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

Referenceopen allclose all

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:
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 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.
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.

Additional information

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.