2-nitrotoluene

Endpoint summary

Description of key information

The oral LD50 value ranged from 890 to 2546 mg/kg b.w. in rats

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment

Principles of method if other than guideline:

Single oral dose toxicity was determined by the method of Smyth et al., Am. Ind. Hyg. Ass. J. 30, 470-476 (1962) in which the LD50 and its confidence limits are estimated by the moving average technique (Thompson WR, 1947, Bact Rev 11: 115-145; Weil C.1952, Biometrics 8. 249-263)

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Test type:

acute toxic class method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Weight at study initiation: 200-300g
-Diet: Purina Formulab Chow 5008

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

Not reported

No. of animals per sex per dose:

Not reported

Control animals:

other: not applicable

Statistics:

Probit analysis

Sex:

male

Dose descriptor:

LD50

Effect level:

890 mg/kg bw

95% CL:

500 - 1 580

Interpretation of results:

Category 3 based on GHS criteria

Executive summary:

Vernot (1977):

Single oral dose toxicity was determined by the method of Smyth et al., Am. Ind. Hyg. Ass. J. 30, 470-476 (1962) in which the LD50 and its confidence limits are estimated by the moving average technique (Thompson WR, 1947, Bact Rev 11: 115-145; Weil C.1952, Biometrics 8. 249-263)

LD50 was determined to be 890 mg/kg bw (95% CL: 500-1580).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable deviations

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

No GLP. Fasting and acclimation period, and environmental conditions not reported. Animals weighed just the first days of the treatment. Body weights were not reported.

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Evic-Ceba, 33290 Blanquefort, France
- Weight at study initiation: 200 g (average)
- Diet (e.g. ad libitum): Extralabo M25 Biscuits (Evic-Ceba, France) ad libitum
- Water (e.g. ad libitum): tap water ad libitum

Route of administration:

oral: gavage

Vehicle:

other: olive oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1 mL per 200 g bw

Doses:

1000, 1500, 2000, 2500, 3000, 4000 mg/kg (males);
1000, 1500, 2000, 2500, 3000, 4000 mg/kg (female)

No. of animals per sex per dose:

10

Control animals:

other: not applicable

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The behavior and the symptomatology of the animals were observed every day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, and body weight

Statistics:

The calculation of the LD50 was performed according to the method of Miller and Tainter (Proc Soc Exp Biol Med, 1944, 57: 261-264), following the indications of Bartlett (Suppl I Rog Stat, 1937, 137-170)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 100 mg/kg bw

Mortality:

The mortality was registered within 48 hours, otherwise the recovery is gradual

Clinical signs:

other: other: Soon after the administration of the test substance, the animals were shaking. The animals respiratory rythm was increased. They animals had seizure for short time

Doses mg/kg	Mortality							Mortality rate
	hours			days
Male rats	0-5	5-18	18-24	2	3	4-7	8-14
1000	0	0	0	0	0	0	0	0/10
1500	0	0	1	0	0	0	0	1/10
2000	0	0	2	0	0	0	0	5/10
2500	0	0	5	0	0	0	0	7/10
3000	0	0	6	0	0	0	0	8/10
4000	0	0	10	-	-	-	-	10/10
Female rats
1000	0	0	0	0	0	0	0	0/10
1500	0	0	2	0	0	0	0	2/10
2000	0	0	4	0	0	0	0	4/10
2500	0	0	6	2	0	0	0	8/10
3000	0	0	8	0	0	0	0	8/10
4000	0	0	10	-	-	-	-	10/10

 

Interpretation of results:

Category 5 based on GHS criteria

Executive summary:

Ciss (1980):

The acute toxicity of 2 -nitrotoluene was determinated by oral exposure (gavage) with a method similar to OECD 401 with deviations (No GLP. Fasting and acclimation period, and environmental conditions not reported. Animals weighed just the first days of the treatment. Body weights were not reported).

LD 50 resulted to be 2100 mg/kg bw. Mortality took place with 48 hours from the treatment.

Soon after the administration of the test substance, the animals were shaking. The animals respiratory rythm was increased. They animals had seizure for short time.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

890 mg/kg bw

Quality of whole database:

The lowest LD50 value was selected as the dose descriptor for this endpoint.

Additional information

EU RISK ASSESSMENT 2008

 

The acute toxicity of 2-nitrotoluene has been investigated in rats and mice (inhalatory), rats and rabbits (dermal), and rats, mice and rabbits (oral).

 

The available studies on inhalatory toxicity have limited quality especially with respect to the identity of the test substance (purity not reported). However, because of results were similar they can be useful for risk assessment. At saturated vapour concentrations, 190.8 ppm (1.086 mg/L) for 8 h or 320 ppm (1.795 mg/L) for 4 h in rats and 354 ppm (1.986 mg/L) for 4 h in mice, 2-nitrotoluene, did not produce mortalities, toxicity and gross lesions within 14-day observation period. Therefore, according to the CLP criteria, no classification is necessary.

 

The available studies on dermal toxicity have limited quality especially with respect to the identity of the test substance (purity not reported). However, because of results were similar they can be useful for risk assessment. In a limit test, 2-nitrotoluene (5000 mg/kg b.w. in rats and 20000 mg/kg b.w. in rabbits) did not produce either mortality or toxicity within 14-day observation period. Therefore, according to the CLP criteria, no classification is necessary.

 

The available studies on acute oral toxicity have limited quality (only in one study purity was reported). However, because of results were similar they can be useful for risk assessment. The oral LD50 value ranged from 890 to 2546 mg/kg b.w. in rats, from 970 to 2462 mg/kg b.w. in mice and was determined to be 1750 mg/kg b.w in rabbit. Clinical signs of toxicity were related with methaemoglobin formation. Based on the lower oral LD50 value (890 mg/kg b.w in rats), according to the CLP criteria, 2-nitrotoluene is classified in the Category 4.

 

The reported effects in humans exposed by different routes are most likely due to methaemoglobin formation but data on acute toxicity (Goldblatt, 1955) are limited to inhalation exposure. However, since a NOAEC/LOAEC could not be determined as starting point for risk characterization for acute toxicity because the exposure duration was not reported. Therefore, the risk assessment for acute toxicity has been derived from animal data.

Justification for classification or non-classification

Harmonised classification:

The substance is classified in Category 4 (H302: Harmful if swallowed) according to the Regulation (EC) No. 1272/2008 (CLP).