2-(chloromethyl)-4-methylquinazoline

Endpoint summary

Description of key information

The acute lethal dose (LD50) of the test substance via the oral route was estimated to be 1000 mg/kg bw. Therefore, the substance is classified  as acute oral toxic category 4 (H302).
The acute dermal toxicity was determined to be greater than 2000 mg/kg bw. 

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:

2004-07-01 to 2004-07-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2000

GLP compliance:

yes

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: Charles River Deutschland GmbH, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 7-8 weeks
- Weight at study initiation: males 181-205 g, females 130-140 g
- Fasting period before study: in the afternoon of day -1 (at approx. 16:00 h) over night
- Housing: in groups up to three animals of one gender per cage
- Diet (e.g. ad libitum): ad libitum (Kliba No. 3438.0.25, Provimi Kliba SA, CH-4303 Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): ad libitum (municipal tap water; Stadtwerke Biberach)
- Acclimation period: 5 to 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-2
- Humidity (%): 45 - 75
- Air changes (per hr): min. 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % aqueous hydroxyethylcellulose

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of prior experience, 200 mg/kg bw was chosen as the initial dose. The second dose was selected based on the animals´ response to 200 mg/kg.

Doses:

200, 2000 mg/kg bw

No. of animals per sex per dose:

200 mg/kg bw: 3 female
2000 mg/kg bw: 3 female
200 mg/kg bw: 3 male

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made once to twice daily. Body weight was recorded on Day -1 and during the observation period, the body weight of all animals was recorded on Day 1, 2, 8 and 15, respectively.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight

Statistics:

None performed.

Sex:

male/female

Dose descriptor:

other: ALD

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

200 mg/kg: No mortality occurred in either male or female rats.
2000 mg/kg: Two out of three females died. Two rats were found dead in the morning of Day 2. Due to the marked mortality in females, no male rats were treated.

Clinical signs:

other: 200 mg/kg, male: Clinical signs were observed on Day 1 only in all three rats treated and included piloerection (2.5 h to 5.25 h post administration) and sedation (4.0 h to 5.25 h post administration). Rats returned to normal on Day 1 (6.25 h post adminis

Gross pathology:

200 mg/kg: Except slight changes in the uterus of one female animal (horns filled with aqueous liquid), no gross macroscopic alterations were observed at necropsy.
2000 mg/kg: At necropsy of two female animals, which died on Day 1, gross macroscopic changes were observed in the lungs (discoloration), the stomach (discoloration of the mucosa, multiple bleedings in the wall) and the intestines (empty lumen). One animal, in addition, showed alterations in the skin around the nose (red discharge) and in the liver (stasis).
No changes were seen at necropsy of the female animal, which survived the entire study period.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

according to CLP

Conclusions:

An approximate lethal dose (ALD) for the test item between 200 and 2000 mg/kg in rats was determined.
Based on the dose effect relationship the LD 50 was estimated to be 1000 mg/kg bw according to Annex 3b of the replaced OECD 423, adopted in March 1996. Therefore, the substance has to be classified as harmful if swallowed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 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:

2006-11-27 to 2006-11-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (Europe) Laboratories, Inc. Toxi Coop Ltd. 1103 Budapest, Cserkesz u. 90
- Age at study initiation: Young adult rats
- Weight at study initiation: Male: 236 - 267g; Female: 201 - 221g
- Housing: Individual caging (1 animal/cage)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8-12 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- % coverage: approx. 10 %
- Type of wrap if used: Sterile gauze pads

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing with water was performed
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes (test item in its original form, moistened with 0.5 ml of distilled water)
- Constant volume or concentration used: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of exposure:

24 h

Doses:

single dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on day 0 (beginning of the experiment), on day 7 and on day 14; clinical examination: day of treatment 1h and 5h after the administration and once each day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the test animals died.

Clinical signs:

other: There were no clinical signs. The behaviour and physical condition of animals were considered to be normal. CD 605 caused erythema on the treated skin of male (3/5) and female (5/5) rats, which recovered on days 3 and 4.

Gross pathology:

No macroscopic alterations due to the effects of the test item were found. Gross necropsy revealed pinprick-sized haemorrhages in the lungs both in males (1/5) and in female animals (2/5). The haemorrhages in the lungs were due to the method of anaesthesia and exsanguinations are also observable in untreated animals after anaesthesia.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item does not meet the criteria for classification as a LD50 of > 2000 mg/kg bw was determined.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

The valid acute oral study, conducted according to the revised version of OECD 423 (Acute Oral Toxicity – Acute Toxic Class Method, October 2000), involves gavage administration of two doses (200 and 2000 mg/kg bw) of the test material to groups of male and female rats. Mortality was observed in two of three female rats at 2000 mg/kg bw and no mortality was observed at 200 mg/kg bw in male and female rats. Due to the marked mortality in females, no male rats were treated with 2000 mg/kg. An approximate lethal dose (ALD) for CD 605 between 200 and 2000 mg/kg bw in rats was determined. Based on the dose effect relationship the LD 50 was estimated to be 1000 mg/kg bw according to Annex 3b of the replaced OECD 423, adopted in March 1996.

The valid dermal study was conducted as a limit test at 2000 mg/kg bw according to OECD 402 (February 1987) with 5 male and female rats. In this test no adverse effects were observed, thus a LD₅₀ of >2000 mg/kg bw was determined for male and female rats.

The Acute toxicity study via the inhalation route is not required because data via the oral and dermal route are available and exposure via inhalation route is unlikely given the RMM implemented during use.

Justification for classification or non-classification

As a LD50 value of 1000 mg/kg bw was determined for acute oral toxicity based on a reliable acute toxicity test, the test item is classified according to CLP Regulation (1272/2008) as acute toxicity oral Category 4, H302 (harmful if swallowed).

In the reliable acute dermal test with the test item no adverse effects were observed. Thus, according to CLP Regulation (1272/2008) the substance is not classified for dermal toxicity.

No inhalation study is available.