Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1998-07-07 - 1998-12-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented guideline study in compliance with GLP (conducted with a read-across substance)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: viscous liquid
Details on test material:
- Molecular formula (if other than submission substance): C28H62NO4P (for a representative structure: Phosphoric acid, di(C8)ester, compds with C12 amine)
- Molecular weight (if other than submission substance): 507.76
- Smiles notation (if other than submission substance): CCCCCCCCCCCCN.O=P(O)(OCCCCCCCC)OCCCCCCCC
- InChl (if other than submission substance): InChI=1/C12H27N/c1-2-3-4-5-6-7-8-9-10-11-12-13/h2-13H2,1H3
- Physical state: liquid
- Storage condition of test material: room temperature in the dark
- Other: Data relating to the identity, purity and stability of the test material are the responsibility of the Sponsor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: approximately eight to twelve weeks
- Weight at study initiation: 205 to 225 g (males); 201 to 234 g (females)
- Housing: housed individually in suspended polypropylene cages furnished with woodflakes during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study
- Diet/Water (e.g. ad libitum): free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK)
- Acclimation period: five days
- Others: 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22 °C
- Humidity (%): 50 to 62 %
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: 10
- Type of wrap if used: veterinary clippers

REMOVAL OF TEST SUBSTANCE
- Washing (if done): bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual bodyweights were recorded prior to application of the test material on day 0 and on days 7 and days 14. The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
Statistics:
not applied

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reaction
Signs of skin irritation noted in males were restricted to one animal and included crust formation five to seven days after dosing. Signs of skin irritation noted in females included very slight or well-defined erythema and crust formation one to seven days after dosing.

Any other information on results incl. tables

No effects after dosing were notes (0.5, 1, 2, 3 and 4 hours after dosing). Considering individual dermal reactions, crust formation was reported for one male animals on day 5, 6 and 7 after dosing. Furthermore, crust formation was reported for five females on day 4, 5, 6 and 7 after dosing.

Table 1. Individual Bodyweights and weekly Bodyweight Changes

Dose Level mg/kg

Animal Number

and Sex

Bodyweight (g) at Day Bodyweight Gain (g) During Week
0 7 14 1 2
2000 1-0 Male 205 235 278 30 43
1-1 Male 225 251 290 26 39
1-2 Male 218 250 294 32 44
1-3 Male 216 252 312 36 60
1-4 Male 224 257 309 33 52
2-0 Female 201 205 223 4 18
2-1 Female 215 222 240 7 18
2-2 Female 234 238 256 4 18
2-3 Female 225 225 247 0 22
2-4 Female 212 219 231 7 12

For all treated animals and killed on day 14, no abnormalities during macroscopic observation were reported.

Evaluation of Data

Data evaluations included the relationship, if any, between the animal's exposure to the test material 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 dermal median lethal dose (LD50) of the test material was made.

Evaluation of Skin Reaction

Erythema and Eschar Formation Value

0 - No erythema

1 - Very slight erythema (barely perceptible)

2 - Well-defined erythema

3 - Moderate to severe erythema

4 - formation (injuries in depth)

5 - Severe erythema (beet redness) to slight eschar

Oedema Formation

0 - No oedema

1 - Very slight oedema (barely perceptible)

2 - Slight oedema (edges of area well-defined by definite raising)

3 - Moderate oedema (raised approximately 1 millimetre)

4 - Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)

Any other skin reactions, if present were also recorded.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The acute dermal median lethal dose (LD50) of phosphoric acid, mono- and di-(C8-C10) ester, compds. with C12-14 amine in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. According to Regulation (EC) 1272/2008, the substance is not classified as acutely toxic by dermal route of exposure.
Executive summary:

A OECD Guideline 402 study was performed to assess the acute dermal toxicity of phosphoric acid, mono- and di-(C8 -C10) ester, compds. with C12-14 amine in the Sprague-Dawley CD strain rat in compliance with GLP. A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination. There were no deaths. No signs of systemic toxicity were noted during the study. Signs of skin irritation noted during the study included very slight to well-defined erythema and crust formation. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Sprague- Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.