1,2,4-trichlorobenzene

Endpoint summary

Description of key information

- Acute toxicity Oral: Combined LD50 (rats) = 930 mg/kg bw (OECD 401 / non-GLP / K2) (Bayer, 1982).

- Acute toxicity: Dermal: LD50 (rats) > 5000 mg/kg bw (EU RAR 2003).

- Acute toxicity: Inhalation: no relevant 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:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Analytical purity not reported. Acclimation period not reported. Body weights were not reported.

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 9 (males) - 14 (females) weeks
- Weight at study initiation: 159-173 g (males); 159-172 g (females)
- Fasting period before study: the animals were fasted from 16 to 4 hours before the dosing
- Housing: Rats were housed in number of 5 per cage in Makrolon cages type III
- Diet (e.g. ad libitum): Altromin R 1324, Altromin GmbH, Lage, Germany
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.5 °C
- Humidity (%): 60 ± 5%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light (7am/7pm)



IN-LIFE DATES: From: April To: July 1981

Route of administration:

oral: gavage

Vehicle:

other: cremophore/tap water mixture (1 : 4)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

630-3100 mg/kg

No. of animals per sex per dose:

5

Control animals:

other: not applicable

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice per day and once on weekends and holidays. The animals were weighed at the moment of the exposure, after 1 week, and at the end of the 14-day oberservation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology analysis

Statistics:

The calculation of the LD50 with the confidence interval for p <0.05 was performed with the Probit analysis according to Fink und Hund (Arzneim.-Forsch. 15:1965, 624)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

930 mg/kg bw

95% CL:

>= 840 - <= 1 050

Remarks on result:

other: Slope=9.11

Mortality:

The deaths occurred during the first 3 days of the treatment

Clinical signs:

other: See remark

Body weight:

other body weight observations

Remarks:

body weight was not reported

Gross pathology:

In the section of deceased male and female animals were noted alterations of the stomach and intestine mucous membrane, and gastric bleeding .
The liver had a localized clay colour and showed clear lobe markings. At the end of the test in the dissected male and female animals dosed with 1.0 and 1.25 mg/kg were observed slight alterations of the stomach. All other animals were examined macroscopically unremarkable.

Male
Dose mg/kg	Number of dead animals	Animals with symptoms	Total number of animals employed	Time of death
630	0	0	5
730	1	5	5	2^ndday
800	3	5	5	2^nd-3^rdday
1000	3	5	5	2^ndday
1250	5	5	5	24 hours-2^ndday
1600	5	5	5	24 hours
3100	5	5	5	24 hours
Female
Dose mg/kg	Number of dead animals	Animals with symptoms	Total number of animals employed	Time of death
630	0	0	5
730	0	5	5
800	2	5	5	3^rdday
1000	3	5	5	2^nd-3^rdday
1250	3	5	5	24 hours-2^ndday
1600	5	5	5	24 hours-2^ndday
3100	5	5	5	24 hours

 

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

Groups of 5 rats of each sex with starting weights between 159 g and 173 g were given 1,2,4-trichlorobenzene (630-3100 mg/kg) by gavage according to OECD guideline 401 with deviations (Analytical purity not reported. Air changes not reported. Acclimation period not reported.Body weights not reported).

The LD50 was 930 mg/kg with 95% confidential limit of 840-1050.

The deaths occurred during the first 3 days of the treatment.

The oral single doses from 730 to 3100 mg/kg provoked the following poisoning symptoms: worsening of the general conditions, sedation, necrosis, side-prone position.

In the section of deceased male and female animals were noted alterations of the stomach and intestine mucous membrane, and gastric bleeding.

The liver had a localized clay colour and showed clear lobe markings. At the end of the test in the dissected male and female animals dosed with 1000 and 1250 mg/kg were observed slight alterations of the stomach. All other animals were examined macroscopically unremarkable.

On the basis of theses findings it is possible to classify 1,2,4 -trichlorobenzene in Category 4 (Acute Tox. 4, H302 according to GHS.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

930

Quality of whole database:

One key study available (Bayer, 1982), comparable to guideline study. Other available data report similar LD50, all within the CLP Category 4 range.

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:

other: EU Risk Assessment

Adequacy of study:

other information

Reliability:

other: EU Risk Assessment

Rationale for reliability incl. deficiencies:

other: no reliability is given as this is a summary entry for the EU RAR

Principles of method if other than guideline:

EU Risk Assessment

GLP compliance:

not specified

EU Risk Assessment (2003):

Some studies on acute dermal toxicity are summarized in EU Risk Assessment.

Some of these studies were reliable studies with restrictions or reliability was not assignable because references were only cited as secondary literature.

Four rats of each sex were exposed for 24 hours with undiluted 98% pure 1,2,4-TCB in an occlusive bandage on the dorso-lumbar region. An LD50 of 6,139 mg 1,2,4-TCB/kg (4299-9056 mg/kg, 95% confidence limits) was estimated. The signs of intoxication were depression of activity at low doses and pre-death extensor convulsions at lethal dose levels. All deaths occurred within 5 days of exposure. Autopsies of the animals that died and those killed after the 10-day observation period revealed no pathological lesions attributable to the compound (Brown et al., 1969).

The acute dermal LD50 in rabbits for pure 1,2,4-TCB is approximately 5,000 mg/kg (Dow

Chemical, 1982) and >5,000 mg/kg for technical 1,2,4-TCB (Dow Chemical, 1980).

A study in ddY mice using 10 animals of each sex per group reporting the acute dermal toxicity gave values of 300 mg/kg (243-369 mg/kg, 95% confidence limits) for males and 305 mg/kg (247-375 mg/kg, 95% confidence limits) for females (Yamamoto et al., 1978). There is no obvious explanation for the very low value for the LD50 found in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

>= 5 000 mg/kg bw

Quality of whole database:

No key study identified, but the rabbit study reported in the EU RAR showed a LD50 > 5000 mg/kg bw.

Additional information

Acute toxicity: Oral

A key study was identified (Bayer, 1982). In this study performed according to OECD TG 401, the rat (combined) LD50 was 930 mg/kg bw with 95% confidential limit of 840-1050 mg/kg bw. The oral single doses from 730 to 3100 mg/kg bw provoked the following poisoning symptoms: worsening of the general conditions, sedation, necrosis, side-prone position.The deaths occurred during the first 3 days of the treatment. In the section of deceased male and female animals noted alterations were of the stomach and intestine mucous membrane, and gastric bleeding. The liver had a localized clay colour and showed clear lobe markings. At the end of the test in the dissected male and female animals dosed with 1000 and 1250 mg/kg were observed slight alterations of the stomach. All other animals were examined macroscopically unremarkable.

 In the EU RAR, rats LD50 ranging between 880 and 1421 mg/kg bw/day were reported.

 

Acute Toxicity: Dermal

In the EU RAR, rabbits LD50 was reported to be > 5000 mg/kg bw.

 

Acute Toxicity: Inhalation

In the EU RAR, no mortality was reported at concentration of 3.1 mg/L/4hr. As no higher concentration was tested it was not possible to determine a LC50.

Justification for classification or non-classification

Harmonised classification:

The substance is classified as Harmful if swallowed (H302) according to the Regulation (EC) No. 1272/2008 (CLP 000)

The substance has no harmonised classification for acute toxicity via dermal route or inhalation according to the CLP. 

 

Self classification:

Acute toxicity via Oral route:

Based on the available information, the substance is classified in Category 4 according to the CLP and to the GHS as the LD50 is in the range 300-2000 mg/kg bw.

Acute toxicity via Dermal route: 

Based on the available information, the test item is not classified according to the CLP and the GHS as the LD50 is greater than 5000 mg/kg bw 

Acute toxicity via Inhalation:

No study is available. 

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required. 

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study. 

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C ≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw ≥ C > 1000 mg/kg bw). No classification is required. 

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study. 

Specific target organ toxicity: single exposure (Inhalation):

No study is available. 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.