Alkenes, C11-14, hydroformylation products, distn. residues, reaction products with maleic anhydride and sodium bisulfite, sodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 07 August 2012 and 06 September 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

No analysis was carried out to determine the homogeneity, concentration or stability of the test item formulation. This exception is considered not to affect the purpose or integrity of the study.

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Alkenes, C11-14, hydroformylation products, distn. residues, reaction products with maleic anhydride and sodium bisulfite, sodium salts

EC Number:

938-654-2

Molecular formula:

not applicable

IUPAC Name:

Alkenes, C11-14, hydroformylation products, distn. residues, reaction products with maleic anhydride and sodium bisulfite, sodium salts

Test material form:

other: solid

Details on test material:

Sponsor's identification: Alkenes hydroformylated, sulfosuccinates, sodium salt
Description : off white solid
Batch number : Rif.7018
Purity : Not supplied
Date received : 27 April 2012
Expiry date : 31 May 2013
Storage conditions: approximately - 20°C in the dark
The integrity of supplied data relating to the identity, purity and stability of the test item is the responsibility of the Sponsor.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group.
The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe.

Doses:

300 mg/kg
2000 mg/kg

No. of animals per sex per dose:

3 females @ 300 mg/kg
6 females @ 2000 mg/kg

Control animals:

no

Details on study design:

In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Groups of fasted animals were treated as follows:
Dose Level (mg/kg) Concentration (mg/ml) Dose Volume (ml/kg) Number of Rats (Female)
300 30 10 3
2000 200 10 3
2000 200 10 3
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
The sequence of dosing may not always follow the Test Guideline as shown in the schematic diagram in Appendix 1. It is Company Policy to minimise the number of animals used on each study in accordance with UK Government Home Office guidelines. The sequence of testing does not affect the final classification of the test item.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed in the study

Mortality:

Individual mortality data are given in Table 1.
There were no deaths.

Clinical signs:

other: Individual clinical observations are given in Table 2 and Table 3. There were no signs of systemic toxicity.

Gross pathology:

Individual necropsy findings are given in Table 6 and Table 7.
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Evaluation of Data

Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD₅₀) of the test item was made as shown in the schematic diagram in Appendix 1 (attachment 1)

Table 1              Mortality Data

Dose Level mg/kg	Sex	Number of Animals Treated	Deaths During Day of Dosing (Hours)				Deaths During Period After Dosing (Days)								Deaths
			½	1	2	4	1	2	3	4	5	6	7	8-14
300	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
2000	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3

Table 2              Individual Clinical Observations -300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0= No signs of systemic toxicity

Table 3              Individual Clinical Observations -2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0= No signs of systemic toxicity

Table 4              Individual Bodyweights and Weekly Bodyweight Changes -300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	151	168	177	17	9
	1-1 Female	164	193	210	29	17
	1-2 Female	160	184	207	24	23

Table 5              Individual Bodyweights and Weekly Bodyweight Changes -2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	2-0 Female	160	178	194	18	16
	2-1 Female	156	171	180	15	9
	2-2 Female	165	178	189	13	11
	3-0 Female	164	186	195	22	9
	3-1 Female	163	180	197	17	17
	3-2 Female	152	173	179	21	6

Table 6              Individual Necropsy Findings -300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
300	1-0 Female	Killed Day 14	No abnormalities detected
	1-1 Female	Killed Day 14	No abnormalities detected
	1-2 Female	Killed Day 14	No abnormalities detected

Table 7              Individual Necropsy Findings -2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Killed Day 14	No abnormalities detected
	3-2 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

Executive summary:

Introduction.The study was performed to assess the acute oral toxicity of the test item following a single oral administration in the Wistar strain rat. The method was designed to be compatible with the following:

OECD Guidelime for the Testing of Chemicals No.423 "ACute Oral Toxicity - Acute Toxic Class Method" (adopted 17 December 2001)

Method B1 tris Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method. A group of three fasted females was treated with the test item at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at a dose level of 2000 mg/kg bodyweight. Dosing was performed sequentially.

The test item was administered orally as a solution in distilled water. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System ‑ Unclassified).