Reaction mass of (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl palmitate and (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl stearate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

445-990-9

EC Name:

-

Cas Number:

376588-17-9

Molecular formula:

C38 H71 N O6

Test animals

Species:

rat

Strain:

other: HanBrI: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: Males: 9-10 weeks; Females: 12-13 weeks
- Weight at study initiation: Males: 235-275 g; Females: 180-200 g
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 84/02 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum.
- Water: Community tap water from FQllinsdorf acf libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 10-70
- Air changes (per hr): 10-15
- 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: the backs of the animals
- % coverage: 10
- Type of wrap if used: gauze patch with a semi-occlusive dressing fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm tap water and dried with disposable paper towels
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2g/kg bodyweight

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. During days 2-15 twice daily for viability and once daily for clinical signs.
- Frequency of weighing: On test days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, viability

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

Individual body weights in grams

Sex / dose	Animal No.	Day of treatment	Day 8	Day 15
male / 2000 mg/kg	1	236.4	249.3	267.7
	2	269.3	285	298.6
	3	271.5	29.38	318.8
	4	243.4	266.0	287.2
	5	254.4	280.3	301.1
female / 2000 mg/kg	1	180.5	184.8	182.1
	2	186.6	194.8	197.7
	3	186.9	185.2	197.1
	4	194.5	201.4	211.3
	5	197.0	208.4	216.6

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

The acute dermal LD50 of the test substance in rats of both sexes is greater than 2000 mg/kg body weight.

Executive summary:

Five male and five female HanBrI: WIST (SPF) rats were treated with the test substance at 2000 mg/kg by dermal application. The test item was applied undiluted as delivered from the sponsor at an amount dosage of 2 g/kg. The application period was 24 hours. No deaths occurred during the study. No clinical signs were observed during the observation period. One female animal showed a loss of body weight (0.9 %) one week after treatment. It recovered between test day 8 and the end of the observation period. Another female animal lost body weight (1.5 %) from test day 8 to 15. The body weight of the remaining animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

In conclusion, the median lethal dose of the test substance after single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.