6-Amino-5-chloro-2-cyclopyrimidine-4-carboxylic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 March - 17 May 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted (according to study report) 1987

Deviations:

yes

Remarks:

Limit dose higher than 2000 mg/kg bw/day (5000 mg/kg bw/day)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

1

Reference substance name:

6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid

EC Number:

617-769-9

Cas Number:

858956-08-8

Molecular formula:

C8H8ClN3O2

IUPAC Name:

6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina, USA
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: approximately 9 weeks (males), 10 weeks (females)
- Weight at study initiation: 290.2 g (males), 225.5 g (females)
- Housing: individually in stainless steel, wire-mesh cages suspended above cage boards
- Diet: water, ad libitum
- Water: PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 -26
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: shaved back from the scapular to the lumbar region (approximately 5 cm x 7.4 cm, 37 cm²)
- Type of wrap if used: test substance was covered with a 2-ply gauze patch. Rats were then wrapped with stretch gauze bandage and self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 5000 mg/kg bw moistened with 0.6 mL of deionized water
- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

5000 mg/kg bw/day

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and clinical signs of illness, injury, dermal irritation and abnormal behavior were made daily (weekends excluded for dermal irritation). Body weight was determined prior to treatment and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight other: dermal irritation (Draize score)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the 14 days test period.

Clinical signs:

other: No clinical signs of systemic toxicity were observed during the study period. Two male rats exhibited stained fur/skin or ocular discharge after test substance removal. These clinical signs are commonly seen in wrapped rats and therefore are not considere

Gross pathology:

Gross pathology did not reveal any abnormalities.

Other findings:

- Other observations: Erythema (score of 1 or 2) was observed in 9 rats and ulceration was observed in 4 rats on the day after application of the test substance. The erythema and ulceration may have been due to the gauze pads adhering to the test sites at the time of washing. No dermal irritation was observed in the remaining rat.

Any other information on results incl. tables

Table 1. Table for acute dermal toxicity.
Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
5000	0/5/5	stained (red) skin/fur chin, ulceration, black discharge eye bilateral, Day 1	/	0
Females
5000	0/1/5	Hair loss (forelimb bilateral), Day 11 -14	/	0
LD50 = > 5000 mg/kg bw
* first number = number of dead animals
second number = number of animals with clinical signs
third number = number of animals used

Table 1. Results of skin irritation parameters (Draize score)
Observation time	Rabbit no.
	1 (male)		2 (male)		3 (male)		4 (male)		5 (male)		6 (female)		7 (female)		8 (female)		9 (female)		10 (female)
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 Day	0	0	2	0	2	0	2	0	2	0	1	0	1	0	2	0	1	0	2	0
Day 2-14	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

In this acute dermal toxicity study a LD50 value of > 5000 mg/kg bw was determined in male and female rats.