Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Oral: LD50 = 1625 mg/kg body weight leading to classification as Acute Toxicity Hazard Category 4 according to CLP
Dermal: LD50 > 2000 mg/kg body weight leading to no classification according to CLP
Inhalation: no information available

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Limited, Wyton, Huntingdon
- Age at study initiation: 5 - 8 weeks
- Weight at study initiation: males: 132 -197 g, females 134 -175 g
- Fasting period before study: overnight fast immediately before dosing and for 2 hours after dosing
- Housing: in groups of up to 5 by sex in polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): mains drinking water ad libitum
- Acclimation period: >= 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40 -68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 1985-10-25
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 3.7 mL/kg
Doses:
2000 mg/kg

As treatment-related mortalities occurred, the following doses were tested in addition:
500 mg/kg
1000 mg/kg
4000 mg/kg
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 1 and 4 hours after dosing and subsequently once daily for 14 days, weighing on day of treatment and day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy
Statistics:
Method of Weil C.S. (1952) Biometrics 8,249 to calculate LD50 an 95 % confidence limits
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
95% CL:
1 587 - 2 520
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 625 mg/kg bw
Based on:
test mat.
95% CL:
1 231 - 2 144
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 4 000 mg/kg bw
Based on:
test mat.
Mortality:
500 mg/kg: 0/10
1000 mg/kg: 0/10
2000 mg/kg: 5/10 (1 male died on day 0, 3 males on day 1, 1 female on day 1)
4000 mg/kg: 10/10 (5 males died on day 0, 3 females on day 0, 2 females on day 1)
Clinical signs:
other: 500 mg/kg: Signs of hunched posture, pilo-erection and lethargy during day of dosing. All animals were normal on day 1. 1000 mg/kg: Hunched posture, pilo-erection, lethargy, decreased respiratory rate, occasional signs of increased salivation and ptosis
Gross pathology:
500 mg/kg: one male showed a thickened area of the glandular region of the stomach
1000 mg/kg: one male showed an isolated finging of congested lungs.
2000 mg/kg: haemorrhage of the glandular and non-glandular regions of the stomach in animals that died during the study. Other occasional findings were congested lungs, dark livers and kindneys.
4000 mg/kg: Abnormal dark or congested appearances of the heart, lungs, liver, kidneys and spleen. The glandular and non-glandular regions of the stomach were severely haemorrhage with a sloughing of the inner lining. The large and small intestines were als haemorrhaged or congested.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 determined in an acute oral study was 2000 mg/kg bw for males/females, 1625 mg/kg bw for males only and > 2000 mg/kg bw for females only.
Executive summary:

The acute toxicity after oral application of the test substance was investigated in a GLP study according to OECD TG 401. Groups of 5 male and 5 female rats were dosed with 500, 1000, 2000 and 4000 mg/kg bw of the test substance by gavage. They were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. All animals were subjected to gross necropsy examination.

No deaths occurred after application of 500 and 1000 mg/kg bw. The animals showed signs of hunched posture, pilo-erection and lethargy on day 0 but were all normal again on day 1. At necropsy, a thickened area of the glandular region of the stomach was observed in one male treated with 500 mg/kg bw. One male treated with 1000 mg/kg bw showed an isolated finging of congested lungs.

After application of 2000 mg/kg bw, 1 male was dead by day 0 and 3 males and 1 female were dead by day 1. The animals showed clinical signs such as hunched posture, pilo-erection, lethargy, ptosis, decreases resporatory rate and ataxia at the four hour observation. All surviving animlas gradually recovered and were normal 4 -5 days after treatment. In animals that died during the study, haemorrhage of the glandular and non-glandular regions of the stomach were noted at necropsy.

After application of 4000 mg/kg bw, all males and 3 females died on day 0. The remaining 2 females died on day 1. One hour after treatment, the animals showed signs of hunched posture, pilo-erection, leathargy, ptosis, increase salivation and decreased respiratory rate. The two females still alive at the 4 hour observation showed in addition occasional body tremors, ataxia, loss of righting reflex, pallor or the extremities and appeared thin and feeble. At necropsy, abnormal dark or congested appearances of the heart, lungs, liver, kidneys and spleen were observed. The stomach was severely haemorrhaged with a sloughing of the inner lining. The intestine was also haemorrhaged or congested.

In conclusion, the LD50 was determined to be 2000 mg/kg bw for males/females, 1625 mg/kg bw for males only and > 2000 mg/kg bw for females only.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 625 mg/kg bw
Quality of whole database:
One reliable study and three supporting not assignable studies are available.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Not reported
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Animals were given a single application of 2000 mg/kg. Collars were placed on each animal.
Duration of exposure:
Single application, 14 days of observation
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
other: No treatment-related clinical signs were observed
Gross pathology:
No findings
Other findings:
Irritation of the skin was seen at the application site.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value after a single application of methyl benzoate to the skin of male and female rabbits was > 2000 mg/kg. No mortality occurred during the observation period of 14 days.
Executive summary:

The dermal acute toxicity of methyl benzoate was tested under GLP according to OECD TG 402. A single dose of 2000 mg/kg was applied to the skin of healthy male and female rabbits of the strain New Zealand White. Five animals per sex were tested and observed during a period of 14 days after treatment. A collar was placed on the treated animals. No mortality occurred after dermal treatment or during the observation period. Irritation of the skin was noted at the application site. Four male and three female rabbits had reduced body weights on day 1 and one female had reduced body weight during days 4 to 7. No gross findings were reported at necropsy. The LD50 value after a single application of methyl benzoate to the skin of rabbits was greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
Reliable information on acute dermal toxicity is available showing that the dermal LD50 is greater than 2000 mg/kg in rabbits.

Additional information

Oral toxicity:


Methyl benzoate has relatively low acute toxicity in rats with oral LD50 = 1625 mg/kg bw (Jones and Collier, 1985). This classification is supported by LD50 values determined in rats and mice after a single oral application of the substance (see supporting studies).


Dermal toxicity:


Methyl benzoate has low acute toxicity after a single dermal application. The LD50 value was greater than 2000 mg/kg body weight after a single topical application. Also the read across substance benzoic acid shows low dermal acute toxicity and the LD50 value for benzoic acid in rabbits was greater than 5000 mg/kg.


Inhalation toxicity:


No information on the acute inhalation toxicity of methyl benzoate is available. An acute inhalation study is considered scientifically unnecessary.


Human information: No human information is available.


Justification for selection of acute toxicity – oral endpoint
OECD TG 401 conform study performed under GLP and without deviations.

Justification for classification or non-classification

Oral toxicity:


Based on the above-stated assessment of the acute oral toxicity of methyl benzoate, the oral LD50 value of 1625 mg/kg bw leads to the classification as "H302: Harmful if swallowed" according to CLP (Regulation (EC) No 1272/2008).


Dermal toxicity:


No classification is required according to CLP.


Inhalation toxicity:


According to regulation (EC) 1907/2006 Annex XI (weight of evidence), testing for acute inhalation toxicity is not considered to be required, for the following reasons:



  • methyl benzoate has a moderate vapour pressure of 51 Pa at 25°C, which corresponds to 51 Pa / 101325 Pa x 10e6 ppm = 503 ppm saturated vapour pressure corresponding to 2800 mg/m³ or 2.8 mg/L (with a molecular weight of 136.15 g/mol). Thus an acute 4-hour inhalation study would either be carried out at 2.8 mg/L vapour or the limit dose of 5 mg/L aerosol. Assuming a very conservative value of 100% bioavailability, a rat would receive a systemic dose of 0,8 L/min/kg x 240 min x 5 mg/L aerosol = 960 mg/kg.

  • since the acute oral LD50 was higher than this value, it is considered unlikely that mortality would be observed in an acute inhalation study.

  • about possible local respiratory effects, methyl benzoate is not classified for skin or eye irritation and showed no effects on the skin and only slight effects on the eyes. Therefore, methyl benzoate is unlikely to exert a relevant local irritative effect on respiratory mucosal membranes.


Therefore, the performance of an acute inhalation study is considered unnecessary for scientific reasons and methyl benzoate is unlikely to exert effects upon inhalation that would require classification according to CLP (Regulation (EC) No. 1272/2008).