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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
as at 2001
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

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:
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
Body weight:
- a slightly lower body weight gain in 1/4 surviving females between day 1 and day 8 (returning to normal thereafter) when compared to CIT historical control animals

see Table 2 for details
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.