Sodium (3-hydroxy-2-pentylcyclopentyl)acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-12-24 to 2009-11-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline compliant GLP compliant

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

as at 2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

as at 2004

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Mexoryl SBO

IUPAC Name:

Mexoryl SBO

Details on test material:

- Name of test material (as cited in study report): Mexoryl SBO

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Sprague-Dawley Rj: SD (IOPS Han)
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 218 ± 6 g
- Fasting period before study: 18 hours over night prior to treatment, food supplied again 4 h post dosing
- Housing: one to seven animals during acclimation period and one rat (sighting test) or five rats of the same sex and group (main experiment) during the treatment period, polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm), autoclaved sawdust (SICSA, Alfortville, France)
- Diet (e.g. ad libitum): ad libitum, SSNIFF R/M-H pelleted maintenance diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): ad libitum, drinking water filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 to 70
- Air changes (per hr): approx. 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

purified water (prepared at CIT by reverse osmosis)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL, taking into account the purity of the test item, a correction factor of 3.31 was applied.
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: no justification needed for water
- Lot/batch no. (if required): not applicable
- Purity: purified water (prepared at CIT by reverse osmosis)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
- sighting test: 2000 mg/kg bw is the highest applicable dose as described by the OECD guideline
- main test: based on the absence of mortality or severe toxicity in the sighting test

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 in total over sighting and main test

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- clinical signs: frequently during the hours following administration of the test item, daily thereafter
- weighing: just before administration of the test item on day 1 and then on days 8 and 15
- Necropsy of survivors performed: yes, deeply anesthetized by an intraperitoneal injection of sodium pentobarbital and sacrificed by exsanguination and subjected to a macroscopic examination as soon as possible after death (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities)

Statistics:

No, interpretation of results was based on the flow charts of Annex 3 of the OECD Guideline No. 420, 17th December 2001.

Results and discussion

Preliminary study:

Sighting test: dose-level of 2000 mg/kg (one animal):
No clinical signs and no deaths were observed.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Sighting test: dose-level of 2000 mg/kg (one animal):
- no clinical signs and no deaths observed
Main test: dose-level of 2000 mg/kg (four animals):
- one female found dead on day 2, hypoactivity, piloerection and dyspnea prior to its death
- hypoactivity, piloerection and dyspnea on day 1 only in the three other animals

for details see Table 1

Clinical signs:

other: Sighting test: dose-level of 2000 mg/kg (one animal): - no clinical signs observed Main test: dose-level of 2000 mg/kg (four animals): - hypoactivity, piloerection and dyspnea in all animals for details see Table 1

Gross pathology:

- autolysis was noted in the female found dead on day 2
- no apparent abnormalities in the other animals

Other findings:

no

Any other information on results incl. tables

- Table 1: Individual clinical signs and mortality

Time	Animal No.	Mortality	Clinical signs
Sighting test wit 2000 mg/kg bw
15 min - 45 min 2h - 4h D 2 to D 15	01	No
Main test wit 2000 mg/kg bw
15 min 1h 2 h	02-03-04-05	No	Hypoactivity, piloerection
4 h	02-03-04-05	No	Hypoactivity, piloerection, dyspnea
6 h	03	No	Hypoactivity, piloerection, dyspnea
	02-04-05	No	Hypoactivity
D 2*	03	Yes
	02-04-05	No	None
D 2 **
	02-04-05	No	None
D 3 to D 15

min: minutes

h: hour

D : day

*: morning

**: evening

- Table 2: Individual and mean body weight and weekly body weight change of treated rats of the definitive test (g)

Dose-level mg/kg	Volume mL/kg	Sex	Animals	Days
				1	(1)	8	(1)	15	At death
2000	10	Female	01	210	43	253	23	276	na
			02	225	39	264	19	283	na
			03	222	-	-	-	-	216
			04	216	33	249	16	265	na
			05	215	32	247	18	265	na
			M	218	37	253	19	272
			SD	6	5	8	3	9

(1) = body weight gain

M = mean

SD = standard deviation na = not applicable

- = dead animal

- Table 3: Body weight (g) - CIT historical data of control animals dosed by oral route

Volume (mL/kg)	Sex		Days
			1	(1)	8	(1)	15
10	Female	M	201	40	241	17	258
		SD	11	7	15	8	18
		n	30	30	30	30	30

M : mean

(1) : body weight gain SD : standard deviation n : number of animals

CIT Studies / Experimental : CIT/Study Nos. 31103 RDR / January 2006

Completion date 32841 RDR / February 2007

34718 EPR / April 2008

Reference item : Purified water

Volume of administration : 10 mL/kg

Animals

Species, strain : Rat, Sprague-Dawley Rj: SD (IOPS Han)

Breeder : Janvier, Le Genest-Saint-Isle, France

Age on day 1 : 8 weeks

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

At the request of the Sponsor, the acute oral toxicity of the test item was evaluated in rats according to OECD (No. 420, 17th December 2001) and EC (2004/73/EC, B.1bis, 29th April 2004) guidelines and GLP.
Under the experimental conditions of this study, mortality (20%) was observed after a single oral administration of the test item at the dose-level of 2000 mg/kg (in active material).

Executive summary:

The acute oral toxicity of the test item Mexoryl SBO was evaluated in rats according to OECD (No. 420, 17th December 2001) and EC (2004/73/EC, B.1bis, 29th April 2004) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was prepared in purified water and administered by oral route (gavage), under a volume of 10 mL/kg, to one group of five fasted Sprague-Dawley female rats.

A preliminary test (sighting test) preceded the main test. In the sighting test, the test item was administered at the dose-level of 2000 mg/kg (in active material) to one animal. As no mortality occurred at this dose-level, the test item was administered at the dose-level of 2000 mg/kg (in active material) in the main test.

Clinical signs and mortality were checked for a period of 14 days following the single administration of the test item. The animals were checked for body weight gain and were subjected to necropsy. The interpretation of results was carried out according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations).

Sighting test: dose-level of 2000 mg/kg (one animal) No clinical signs and no deaths were observed. Main test: dose-level of 2000 mg/kg (four animals) One female was found dead on day 2. Hypoactivity, piloerection and dyspnea were noted prior to its death. The same systemic clinical signs were also noted on day 1 only, in the three other animals. When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/4 surviving females between day 1 and day 8 (returning to normal thereafter). The body weight gain of the other surviving animals was not affected by treatment with the test item. At necropsy, advanced autolysis was noted in the female found dead on day 2. No apparent abnormalities were observed in any animal.

Under the experimental conditions of this study, mortality (20%) was observed after a single oral administration of the test item at the dose-level of 2000 mg/kg (in active material).

According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) and CLP as implementation of UN GHS in the EU (Rgegulation (EC) No 1272/2008 of the European Parliament and of the Council, concerning the potential toxicity by oral route, the test item should not be classified.