2,3,3-trimethyl-3H-indole-5-carboxylic acid

Endpoint summary

Description of key information

Acute oral toxicity: discriminating dose >5000 mg/kg bw; RL2; GLP; No effects were observed at the dose of 3100 mg/kg bw. Animals showed slight clinical signs after 1 day (males) and 2 days (females) of application of the 5000 mg/kg bw dose; all effects fully reversed after 72 hours of application.

Acute dermal toxicity: no study available

Acute inhalation toxicity: no study 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

Study period:

1988-09-12 to 1988-10-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

Official Journal L 251 , 19/09/1984 P. 96

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

OECD 401, adopted 1987-02-24

Deviations:

no

GLP compliance:

yes

Remarks:

Deviations: no quality assurance implemented for conduct and reporting of test; no analytical test on stability of test substance due to short period between preparation and dosage; deviations do not have an impact on the testing results.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMA
- Source: WISW (SPF Cqb), Winkelmann, Borchen
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks (male), 10 weeks (female)
- Weight at study initiation: 165 g (mean; male), 170 g (mean; female)
- Fasting period before study: yes (16 h before and 4 h after application)
- Housing: Makrolon cages (type III), 5 rats per cage
- Diet (e.g. ad libitum): Altromin 1324 pellets
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 31%, 50%
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

Two groups with two different doses (3100 mg/kg bw; 5000 mg/kg bw) and 5 males and 5 females per group.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several observations at day of application followed by twice a day (once at weekends/bank holidays)
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

0 %

Clinical signs:

other: Slight clinical signs (bad general condition, sedation, bristled fur, increased diuresis) in all males and females of both dose groups from 1st day (males) and 2nd day (females) after application. All clinical signs were observed to be completely reversed

Gross pathology:

No pathological anatomical signs were observed in any animal of both dose groups.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Trimethylcarbonsäure in male and female rats was >5000 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to EU Method B.1, as published on 19 September 1984 and equivalent to OECD Guideline 401, two dose groups, each with 5 males and 5 females, fasted, 8 -10 weeks old Wistar strain rats given a single oral dose of Trimethylcarbonsäure in Propylene glycol by gavage at a dose of 3100 mg/kg bw and 5000 mg/kg bw and observed for 14 days.

No animal died during the observation period. Slight clinical signs observed in all animals at first until 3rd day of application included bad general condition, sedation, bristled fur, increased diuresis. All clinical signs completely reversed at end of day 3 after application.

Female rats of both dose groups showed a decrease in growth rate in study week 2.

No pathological anatomical signs were observed in any animal of both dose groups.

Oral LD50 (rat, males/females) > 5000  mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

According to Commission Regulation (EU) 2016/863 of May 2016 acute toxicity testing by the dermal route (Annex VII, point 8.5.3., column 2) ‘does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure.

The registered substance conforms with the requirements given above. Therefore, it can be concluded for acute dermal toxicity that the available information is conclusive for non-classification.

Justification for classification or non-classification

Based on the available relevant and reliable data, the test substance does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 with respect to acute oral toxicity.

No studies are available for acute dermal and acute inhalation toxicity. According to Commission Regulation (EU) 2016/863 of May 2016 acute toxicity testing by the dermal route (Annex VII, point 8.5.3., column 2) ‘does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure'. The registered substance conforms with the requirements given above. Therefore, it can be concluded for acute dermal toxicity that the available information is conclusive for non-classification.