Methyl 2,4-dihydroxy-3,6-dimethylbenzoate

Endpoint summary

Description of key information

Acute oral toxicity: OECD TG 401: > 5000 mg/kg bw.

Acute dermal toxicity: OECD TG 402: > 5000 mg/kg bw

Acute inhalation: no adverse effects predicted based on low oral toxicity, low vapour pressure and the substance has a minor respirable fraction (ca. 5%).

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

Study period:

15 February, 1980 - 29 February, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Study is not conducted under GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

No details on test material, no purity, no details on environmental conditions.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Albino (TacN (SD) fBR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Farms (Germantown, N.Y.)
- Age at study initiation: Young adults
- Weight at study initiation: males: 160 - 200 g; females: 188 - 210 g
- Fasting period before study: Overnight
- Housing: Singly housed in wire cages
- Diet: Free access to Purina Rodent Laboratory Chow 5001
- Water: Free access to water
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
No data.

Route of administration:

oral: gavage

Vehicle:

ethanol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.0 mL/100 g body weight

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality and pharmacotoxic signs at 1, 3, 5 and 24 hours following dosing and twice daily (once daily on weekends) for the remainder of the 14 day observation period. Surviving animals were weighed at the end of the observation period.
- Necropsy of survivors performed: yes, the animals were killed using ether inhalation.

Statistics:

Not performed.

Preliminary study:

Two fasted rats (one of each sex) received a dose of 5000 mg/kg bw. There were no deaths over the 72 hour observation period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: There were no pharmacotoxic signs in any animal dosed. All the animals appeared normal in health and behaviour throughout the fourteen day observation period.

Gross pathology:

There were no signs indicative of toxicity in any of the ten animals necropsied at termination.

Interpretation of results:

other: not classified

Remarks:

According to EU CLP (EC 1272/2008 and its amendments_.

Conclusions:

The acute oral toxicity test showed an LD50 of >5000 mg/kg bw.

Executive summary:

In this study performed equivalent to OECD TG 401 guideline without GLP, 20 rats (10 males and 10 females) were administered to the substance at a dose level of 5000 mg/kg bw. No deaths occurred. There were no toxicological otoxic signs in any animal dosed. All the animals appeared normal in health and behaviour throughout the fourteen day observation period. The animals all gained weight in a normal pattern. There were no signs indicative of toxicity in any of the ten animals necropsied at termination. The acute oral LD50 for the substance in male and female rats was determined to be >5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Study period:

04 March, 1980 - 18 March,1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Study is not conducted according to GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

No details on test material, no purity, no details on environmental conditions, test site not covered.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Albino (Sprague-Dawley CD strain)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Labs (Wilmington, Mass.)
- Age at study initiation: Young adults
- Weight at study initiation: Males: 205 - 252 g; Females: 188 - 212 g
- Housing: Singly housed in wire cages
- Diet: Free access to Purina Rodent Laboratory Chow 5001
- Water: Free access to water
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
No data.

Type of coverage:

open

Vehicle:

ethanol

Details on dermal exposure:

TEST SITE
- Area of exposure: The site of application was approximately that area bounded by the nape of the neck, the mid dorsum between pectoral and pelvic girdles and the lateral aspects of the scapulae.
- % coverage: Judged to comprise less than 30%
- Type of wrap if used: None, open.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None, any excess material was removed by wiping with a clean cloth.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.0 mL/100 g body weight

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

8

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality and pharmacotoxic signs at 1, 3, 5 and 24 hours following dosing and twice daily (once daily on weekends) for the remainder of the 14 day observation period. Surviving animals were weighed at the end of the observation period.
- Necropsy of survivors performed: yes, the animals were killed using ether inhalation.

Statistics:

Not performed.

Preliminary study:

Two rats (one of each sex) received a dose of 5000 mg/kg bw. There were no deaths over the 72 hour observation period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: There were no clinical signs of toxicity in any animal dosed. All the animals appeared normal in health and behaviour throughout the fourteen day observation period.

Gross pathology:

There were no signs indicative of toxicity in any of the animals necropsied at termination.

Interpretation of results:

other: not classified

Remarks:

According to Regulation (EC) No. 1272/2008.

Conclusions:

The acute dermal toxicity test showed an LD50 of >5000 mg/kg bw.

Executive summary:

In this study performed equivalent to OECD TG 402 guideline without GLP, 16 rats (8 males and 8 females) were administered to the substance at a dose level of 5000 mg/kg bw. No deaths occurred.

There were no clinical signs of toxicity in any animal dosed. All the animals appeared normal in health and behaviour throughout the fourteen day observation period.

The animals all gained weight in a normal pattern. There were no signs indicative of toxicity in any of the animals necropsied at termination.

The acute dermal LD50 for the substance in male and female rats was determined to be >5000 mg/kg bw and the substance does not have to be classified for acute toxicity by the oral route according to Regulation (EC) No. 1272/2000 and GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute dermal toxicity result is of sufficient quality and adequate for this dossier.

Additional information

Acute oral toxicity:

In this study performed equivalent to OECD TG 401 guideline without GLP, 20 rats (10 males and 10 females) were administered to the substance at a dose level of 5000 mg/kg bw. No deaths occurred. There were no toxicological signs in any animal dosed. All the animals appeared normal in health and behaviour throughout the fourteen day observation period. The animals all gained weight in a normal pattern. There were no signs indicative of toxicity in any of the ten animals necropsied at termination. The acute oral LD50 for the substance in male and female rats was determined to be >5000 mg/kg bw.

Acute inhalation:

Acute inhalation is not expected in absence of acute oral toxicity > 5000 mg/kg bw even when there would be some inhalation exposure. In addition, the substance is a solid and contains a minor particle size fraction of < 10 um (5.3% ) based on which the respirable fraction is minor. Also based on vapour pressure of 0.002 Pa inhalation exposure is not expected (< 0.01 Pa).

Acute dermal:

In this study performed equivalent to OECD TG 402 guideline without GLP, 16 rats (8 males and 8 females) were administered to the substance at a dose level of 5000 mg/kg bw. No deaths occurred. There were no clinical signs of toxicity in any animal dosed. All the animals appeared normal in health and behaviour throughout the fourteen day observation period. The animals all gained weight in a normal pattern. There were no signs indicative of toxicity in any of the animals necropsied at termination. The acute dermal LD50 for the substance in male and female rats was determined to be >5000 mg/kg bw.

Justification for classification or non-classification

The substance does not have to be classified for acute toxicity by the oral, inhalation and dermal route according to EU CLP (EC No. 1272/2008 and its amendments).