2,6-diethyl-p-toluidine

Endpoint summary

Description of key information

The test item was tested in acute studies by oral and dermal application on rats. Both studies were conducted in accordance with GLP and following OECD-guidelines. Significant substance-related effects were observed in both tests, therefore the test item needs to be classified as "harmful".

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:

April 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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 ANIMALS
- Source: Winkelmann, Borchen (Germany)
- Strain: Bor: WISW (SPF Cpb)
- Age at study initiation: Males 8 weeks and females 10 weeks
- Weight at study initiation: mean males 190 g and females 171 g
- Fasting period before study: 16 hours before treatment
- Housing: gang housing à 5 animals per cage and sex
- Diet (e.g. ad libitum): Altromin® 1324 Pellets (manufacturer: Altromin GmbH und Co KG, Lage, Germany)
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 10%
- Air changes (per hr): 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours (6 hours artificial light)

Route of administration:

oral: gavage

Vehicle:

peanut oil

Doses:

200, 312, 630, 1000 and 2000 mng/kg

No. of animals per sex per dose:

5 animals per sex and dose

Control animals:

no

Preliminary study:

no pretest

Sex:

male/female

Dose descriptor:

LD50

Effect level:

443 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

630 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

312 mg/kg bw

Based on:

test mat.

Mortality:

200 mg/kg:
No mortality was observed in both sexes.

312 mg/kg:
No mortality was noted in males, whereas one female was found dead five days after treatment.

630 mg/kg:
Four out of five male animals were found dead between days 1 to 4 after dosing. All females died within two to three days after treatment.

1000 mg/kg and 2000 mg/kg:
All males and females died within 2 days after dosing.

Clinical signs:

other: 200 mg/kg: Salivation and ruffled fur was noted in some animals. 312 mg/kg up to 2000 mg/kg: In addition to salivation and ruffled fur, males and females aat these dose levels showed also sedation, gasping, chromodacryorrhoe, tremor, unsteady gait and ov

Gross pathology:

200 mg/kg:
One surviving male showed pale discolored kidneys.

312 mg/kg:
No treatment-related findings observed.

630 mg/kg up to 2000 mg/kg:
Aerogastria, red or black discoloured mucuous mebranes of the stomach and small intestines were noted in both sexes. Females died at 630 mg/kg also showed pale discolored livers. There were some further findings in one died male and in one surviving male.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 on Wistar rats was found to be 443 mg/kg.

Executive summary:

The acute oral LD50 study was conducted as GLP-study according to OECD no. 401. The test was performed as full test on male and female Wistar rats with doses of 200, 312, 630, 1000 and 2000 mg/kg. Mortality occured at concentrations of 312 mg/kg and above, slight to moderate clinical symptoms were noted in almost all dose groups, body weight gain was slightly reduced in surviving males at 312 mg/kg and above. At necrospy, a number of treatment-related effects were noted, such as salivation, ruffled fur, discolored kidneys and liver etc. in all dose groups.

Therefore, based on the oral LD50 of 443 mg/kg, the test item has to be classified as harmful.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

443 mg/kg bw

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:

experimental study

Adequacy of study:

key study

Study period:

April - June 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

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 ANIMALS
- Source: Winkelmann, Borchen (Germany)
- Strain: Bor: WISW (SPF Cpb)
- Age at study initiation: Males ca. 10 weeks and females ca. 15 weeks
- Weight at study initiation: mean males 253 g and females 215 g
- Fasting period before study: 16 hours before treatment
- Housing: gang housing à 5 animals per cage and sex
- Diet (e.g. ad libitum): Altromin® 1324 Pellets (manufacturer: Altromin GmbH und Co KG, Lage, Germany)
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

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

Type of coverage:

semiocclusive

Vehicle:

peanut oil

Duration of exposure:

24 hours

Doses:

100, 1000 and 2000 mg/kg

No. of animals per sex per dose:

5 animals per sex and dose

Control animals:

no

Preliminary study:

Due to high mortality observed in an acute oral toxicity study on rats, 100 and 1000 mg/kg were tested in addition to the limit dose of 2000 mg/kg.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

1 703 mg/kg bw

Based on:

test mat.

Mortality:

100 mg/kg:
No mortality was observed in both sexes.

1000 mg/kg:
No mortality was noted in males, whereas one female was found dead four days after treatment.

2000 mg/kg:
One out of five male animals was found dead on day 4 after dosing. Three out of five females after 3-4 days after dosing.

Clinical signs:

other: 100 mg/kg: No treatment-related effects observed. 1000 mg/kg and 2000 mg/kg: Most of males and females at these dose levels showed gasping, dyspnea, chromodacryorrhoe, unsteady gait, bloody snouts and overall bad condition. Clinical signs appeared four

Gross pathology:

Animals found dead showed red discolored lungs, bllody snouts and small intestines partly discolored black.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 on female Wistar rats was found to be 1703 mg/kg.

Executive summary:

The acute dermal LD50 study was conducted as GLP-study according to OECD no. 402. The test was performed as full test on male and female Wistar rats with doses of 100, 1000 and 2000 mg/kg. Mortality occured at concentrations of 1000 mg/kg and above, slight to moderate clinical symptoms were noted in mid and high dose groups, body weight gain was slightly reduced in all dose groups. At necrospy, a number of treatment-related effects were noted, such as tremor, dyspmea, bloody snouts etc. were recorded in all dose groups.

Therefore, based on the dermal LD50 of 1703 mg/kg in female rats, the test item has to be classified as harmful..

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 703 mg/kg bw

Additional information

Key study: Acute toxicity – oral

The GLP-study was carried in accordance with EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity). Five dose groups were tested per sex. 5 males and 5 females were treated by gavage with doses from 200 up to 2000 mg/kg. Mortality occured at concentrations of 312 mg/kg and above, slight to moderate clinical symptoms were noted in almost all dose groups, body weight gain was slightly reduced in surviving males at 312 mg/kg and above. At necrospy, a number of treatment-related effects were noted, such as salivation, ruffled fur, discolored kidneys and liver etc. in all dose groups. In conclusion, the acute oral LD50 was determined to be 443 mg/kg and the test item has to be classified as harmful.

Key study: Acute toxicity – dermal

The study was conducted as GLP-study according to OECD no. 402. The test was performed as full test on male and female Wistar rats with doses of 100, 1000 and 2000 mg/kg. Mortality occured at concentrations of 1000 mg/kg and above, slight to moderate clinical symptoms were noted in mid and high dose groups, body weight gain was slightly reduced in all dose groups. At necrospy, a number of treatment-related effects were noted, such as tremor, dyspmea, bloody snouts etc. were recorded in all dose groups.

Therefore, based on the dermal LD50 of 1703 mg/kg in female rats, the test item has to be classified as harmful.

Justification for selection of acute toxicity – oral endpoint
GLP study following OECD-guideline; Klimisch 1

Justification for selection of acute toxicity – dermal endpoint
GLP study following OECD-guideline; Klimisch 1

Justification for classification or non-classification

Based on the data available, the substance has to be classified and labelled according to Directive 67/548/EEC (DSD) or Regulation 1272/2008/EC (CLP):

REGULATION (EC) No 1272/2008

Pictogram: Exclamation mark

Signal word: Warning

Hazard statements: H302 - Harmful if swallowed / H312 - Harmful in contact with skin.

Precautionary statements: P280 - Wear protective gloves/ protective clothing/ eye protection/ face protection

P301 + P312 : IF SWALLOWED: Call a POISON CENTER or doctor/ physician if you feel unwell.

67/548/EC - 1999/45/EC

Symbol: Harmful

R-phrases: R21/22 - Harmful in contact with skin and if swallowed.

S-phrases: S24/25 - Avoid contact with skin and eyes.