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Administrative data

Description of key information

The LD50 for acute oral toxicity is > 3227 mg/kg bw.


For acute inhalation toxicity a LD50 = 37.5 mg/l (rat, male) was found. In an additional inhalation study male rats and mice were exposed for 1 hour to 20.583 mg/l of the test substance. None of the animals died.


For the endpoint dermal acute toxicity a Waiver is included since reliable oral and inhalation toxicity studies are available. However,  a supporting study (RL2, Bayer, 1976) shows that the LD50 is >1.08 g/kg bw (rats, limit dose test). This is supported by two non-reliable studies showing LD50 values above 2000 mg/kg bw/d, the limit for classification.

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:
other: in accordance with the guideline
Principles of method if other than guideline:
Single oral application by gavage of 1000, 2500, 2750, 3000, 3500, 4000 or 5000/kg bw (male rats) and 500, 1000, 2500, 3000, 4000 or 5000 mg/kg bw (female rats) in 0.5 ml lutrol/100g bw to 15 male and 15 female Wistar rats per dose. Observation period: 14 d, gross pathological examination, calculation of LD50 by Probit analysis.
Study design similar to OECD TG 401.
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Doses:
Male rats: 1000, 2500, 2750, 3000, 3500, 4000 or 5000 mg/kg bw
Female rats: 500, 1000, 2500, 3000, 4000 or 5000 mg/kg bw
No. of animals per sex per dose:
15
Control animals:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
3 227 mg/kg bw
Mortality:
See table below

Mortality:





















































mg/kg bwMalemg/kg bwFemale
10000/155000/15
25000/1510000/15
27503/1525000/15
30005/1530001/15
350010/15- 
400014/1540009/15
500015/15500014/15

 


Mortality (male rats):
up to 2500 mg/kg bw no rat died
from 2750 mg/kg bw onward dose-related increase in mortality (2750 mg/kg bw: 3/15; 5000 mg/kg bw: 15/15)
Signs of intoxication from 2500 mg/kg bw onwards:
poor condition until the 10th day post application and for at least 3 days accompanied by sedation and difficulties in breathing and at higher doses by quasi-narcotic effects.


LD50 (male rats): 3227 (3060-3430) mg/kg bw


Mortality (female rats)
up to 2500 mg/kg bw no rat died
from 3000 mg/kg bw onward dose-related increase in mortality (3000 mg/kg bw: 1/15; 5000 mg/kg bw: 14/15)
Signs of intoxication from 1000 mg/kg bw onwards:
poor condition until the 10th day post application and for at least 3 days accompanied by sedation and difficulties in breathing and at higher doses by quasi-narcotic effects.
LD50 (female rats): 3860 (3542-4198) mg/kg bw

Interpretation of results:
GHS criteria not met
Conclusions:
Single oral application by gavage to male and female Wistar rats resulted in an LD50 (male rats) of 3227 mg/kg bw and an LD50 (female rats) of 3860 mg/kg bw.

Executive summary:

In a reliable study the substance was applied once by gavage at doses of 1000, 2500, 2750, 3000, 3500, 4000 or 5000/kg bw (male rats) and 500, 1000, 2500, 3000, 4000 or 5000 mg/kg bw (female rats) in 0.5 ml lutrol/100g bw to 15 Wistar rats per sex and dose. The observation period was 14 days. Gross pathological examination was performed and the  LD50 was calculated by Probit analysis.


The LD50 (male rats) was 3227 mg/kg bw, the LD50 (female rats) was 3860 mg/kg bw). At at necropsy 14 days post application a reduced size of abdominal organs, especially liver size was found. Mucus membrane of the stomach with focus of inflammation, stomach content appeared to be bloody.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 227 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented and scientifically acceptable
Principles of method if other than guideline:
10 rats were exposed at various nominal concentrations: 3471, 6402, 8406, 8819 ppm to o-chlorotoluene, observation period: 14 d, calculated LC50
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
not specified
Sex:
male
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
3471, 6402, 8406, 8819 ppm = ca. 18.29, 33.73, 44.30, 46.47 mg/l
No. of animals per sex per dose:
10
Control animals:
not specified
Sex:
male
Dose descriptor:
LC50
Effect level:
7 119 ppm
Exp. duration:
4 h

LC50 value: 7119 (6131-8266) ppm = ca. 37.517 mg/l
clinical signs:
during exposure: hypoactivity, dyspnea, abdominal respiration, exudation from eyes and nose, tremors and prostration, duration: 2-4 days at necropsy: uneven coloration on the surface of the lungs and liver and foci of red and black discoloration on the surface of the lungs.

Interpretation of results:
GHS criteria not met
Conclusions:
Ten male rats were exposed whole body to 3471, 6402, 8406, 8819 ppm = ca. 18.29, 33.73, 44.30, 46.47 mg/l for 4 hours. Clinical signs and mortality were recorded during the exposure and a 14 d post observation period. A necropsy was performed. The LC50 value was 7119 ppm (ca. 37.517 mg/l).
Executive summary:

Ten male rats were exposed whole body to 3471, 6402, 8406, 8819 ppm = ca. 18.29, 33.73, 44.30, 46.47 mg/l for 4 hours. Clinical signs and mortality were recorded during the exposure and a 14 d post observation period. A necropsy was performed. The LC50 value was 7119 ppm (ca. 37.517 mg/l).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
37.5 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: careful observations reported but LD50 value was not reached
Principles of method if other than guideline:
5 rats/sex, hairs removed from the trunk, chemical applied to this prepared area of the skin, single application of 1 ml/kg for 24 hours, during exposure covered with plaster backed with aluminium foil
GLP compliance:
no
Test type:
other: single dose: 1ml/kg bw for 24 hours
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
1 ml/kg bw = 1.08 g/cm³ (density = 1.08 g/cm according LXS MSDS)
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 080 mg/kg bw

Immediately after the application, the animals showed excitation  obviously induced by pain and lasting for up to 2 h, within 24 h difficulty of breathing occurred; the general condition of the animals was reduced up to 8 d after administration of the test  substance; no deaths occurred; after 24 h, the treated areas of skin showed no signs of irritation

Interpretation of results:
GHS criteria not met
Conclusions:
To 5 rats/sex the hairs was removed from the trunk and the chemical applied to this prepared area of the skin. During the single application of 1 ml/kg for 24 hours, the skin was covered with plaster backed with aluminium foil.

Result: LD50 > 1.08 g/kg bw (rat); no death occured
Executive summary:

The chemical was applied to five rats per sex (hairs removed from the trunk). During the single application of 1 ml/kg for 24 hours, the skin was covered with plaster backed with aluminium foil.


Result: LD50 > 1.08 g/kg bw (rat); no death occured. Immediately after application the animals showed excitation for 2 hours, within 24 h difficulty of breathing occured. The general condition of the animals was reduced up to 8 d after administration of the test substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
1.08 mg/kg bw

Additional information

In a reliable acute oral toxicity study (RL 2, similar to OECD TG 401) the substance was applied once by gavage at doses of 1000, 2500, 2750, 3000, 3500, 4000 or 5000/kg bw (male rats) and 500, 1000, 2500, 3000, 4000 or 5000 mg/kg bw (female rats) in 0.5 ml lutrol/100g bw to 15 Wistar rats per sex and dose. The observation period was 14 days. Gross pathological examination was performed and the  LD50 was calculated by Probit analysis. The LD50 (male rats) was 3227 mg/kg bw, the LD50 (female rats) was 3860 mg/kg bw. At necropsy 14 days post application a reduced size of abdominal organs, especially liver size was found. Mucus membrane of the stomach with focus of inflammation, stomach content appeared to be bloody. The result is supported by acute oral toxicity studies in several species (rat, mouse, cat and dog). Non of these studies is rated as reliable, however, taken together, the results support the findings in the key study. 

In a reliable acute inhalation study (RL 2, well documented and scientifically acceptable) rats were exposed to 4 different concentrations to vapour of o-chlorotoluene for 4 hours. A LC50 of 7119 ppm (ca. 37.517 mg/l) for male rats was found. A further valid study on rats and mice was conducted. In both species no death occurred when exposed to 20.583 mg/l air for 1 hour.

In a reliable acute dermal toxicity study which has some limitations rats received a single application of 1 ml/kg bw (highest applied dose) for 24 hours. During exposure the application was covered with plaster backed with aluminium foil. The LD50 was > 1.08 mg/kg bw (rat, limit test).
For the endpoint dermal acute toxicity a Waiver is included since reliable oral and inhalation toxicity studies are available and the reliable acute dermal toxicity studies did not test up to the concentration relevant for classification (2000 mg/kg bw). However,  as outlied above, the limit test showed an LD50 >1.08 g/kg bw, supported by two not assignable studies (secondary literature) on rabbits with LD 50 > 2165 mg/kg bw and LD50 > 7940 mg/kg bw.








Justification for classification or non-classification

Due to the results of the acute oral and dermal toxicity studies a classification according to EU Regulation 1272/2008 (CLP) is not justified.


According to EU Regulation 1272/2008 (CLP), Table 3.1  2-chlorotoluene has a harmonised classificatiuon and is classified for Acute Tox. 4 (inhalation), H 332. Despite the fact that based on the acute inhalation toxicity studies reported here , no classification according to EU Regulation 1272/2008 is warranred, the classification of the test substance for Acute Tox. 4 (inhalation), H 332 will be adopted.