L-gluco-Octitol, 1,5-anhydro-6,8-dideoxy-, (7.xi.)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 November - 14 December 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline 423 with minor deviation: relative humidity in the animal room was sometimes outside of the target range

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

relative humidity in the animal room was sometimes outside of the target range

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material: Mexoryl SBF
- Physical state: Thick brownish paste (very sticky)
- Analytical purity: 92 %
- Lot/batch No.: 003D001
- Date of receipt: 18 November 2005
- Expiration date of the lot/batch: October 2006
- Storage condition of test material: Stored at +4 °C and protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 197 ± 9 g
- Fasting period before study: Animals were fasted for an overnight period of approximately 18 h before dosing, but had free access to water. Food was given back approximately 4 h after administration of the test item.
- Housing: Animals were housed in polycarbonate cages with stainless steel lid. Each cage contained 1-7 animals during the acclimation period and 3 rats of the same group during the treatment period.
- Diet: Adapted pelleted diet SsniffR/M-H (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 µm), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: purified water

Details on oral exposure:

MAXIMUM DOSE VOLUME ADMINISTERED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Dose-level used as the starting dose-level was selected from one of four fixed levels 5, 50, 300 or 2000 mg/kg bw. As the information on the toxic potential of the test item suggested that mortality was unlikely at the highest dose-level, a limit test was performed, using the starting dose-level of 2000 mg/kg bw with three animals.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

- First assay: 3 females
- Confirmatory assay: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
Bodyweight was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: Yes; On Day 15, all animals were killed by carbon dioxide asphyxiation and were subjected to a macroscopic examination.

Statistics:

None

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- No mortality was observed.

Clinical signs:

other: - Piloerection was observed within 2 h of treatment in 3/6 animals. No other clinical signs were noted.

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 7.2.1/1: Individual and mean body weight and weekly body weight change of treated rats (g)

Sex/Dose	Animal no.	Days
		1	(1)	8	(1)	15
First assay: Female/2000 mg/kg bw	1	182	-13	169	66	235
	2	203	1	204	32	236
	3	195	0	195	33	228
	Mean	193	-4	189	44	233
	SD	11	8	18	19	4
Confirmatory assay: Female/2000 mg/kg bw	4	193	43	236	13	249
	5	203	42	245	18	263
	6	204	37	241	23	264
	Mean	200	41	241	18	259
	SD	6	3	5	5	8

(1) = body weight gain; M = mean; SD = standard deviation

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the oral LD50 for Mexoryl SBF is higher than 2000 mg/kg bw in female rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, groups (6 female rats/dose) of Sprague Dawley [Rj: SD (IOPS Han)] rats were given a single oral (gavage) dose of Mexoryl SBF at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. Before the confirmatory test, a sighting test was conducted at the dose-level of 2000 mg/kg bw and animals were observed for 14 days.

No mortality was observed. Piloerection was observed within 2 h of treatment in 3/6 animals. No other clinical signs were noted. During the first week of the study, a reduced body weight gain and a body weight loss were observed in 2/6 and 1/6 animals, respectively, without any relevant consequence at the end of the study. The overall body weight gain of the other treated animals was not affected by treatment with the test item. No macroscopic abnormalities were observed at study termination on Day 15. In this study, the oral LD50 of Mexoryl SBF was considered to be higher than 2000 mg/kg bw in female rats.

Under the test conditions, the oral LD50 for Mexoryl SBF is higher than 2000 mg/kg bw in female rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).