Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., ammonium salts

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 July 2018 - 08 August 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

09 October 2017

Deviations:

yes

Remarks:

The deviation was considered to have not affected the integrity or validity of the study

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Benzenesulfonic acid, 4-sec-decyl, ammonium salts

Molecular formula:

C16H29NO3S

IUPAC Name:

Benzenesulfonic acid, 4-sec-decyl, ammonium salts

Constituent 2

Reference substance name:

Benzenesulfonic acid, 4-sec-undecyl, ammonium salts

Molecular formula:

C17H31NO3S

IUPAC Name:

Benzenesulfonic acid, 4-sec-undecyl, ammonium salts

Constituent 3

Reference substance name:

Benzenesulfonic acid, 4-sec-dodecyl, ammonium salts

Molecular formula:

C18H33NO3S

IUPAC Name:

Benzenesulfonic acid, 4-sec-dodecyl, ammonium salts

Constituent 4

Reference substance name:

Benzenesulfonic acid, 4-sec-tridecyl, ammonium salts

Molecular formula:

C19H35NO3S

IUPAC Name:

Benzenesulfonic acid, 4-sec-tridecyl, ammonium salts

Test material form:

other: Highly viscous light yellow liquid

Details on test material:

Storage Conditions: Highly viscous light yellow liquid

Specific details on test material used for the study:

RADIOLABELLING INFORMATION (if applicable): N/A
- Radiochemical purity:
- Specific activity:
- Locations of the label:
- Expiration date of radiochemical substance:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL:
- Storage condition of test material: At room temperature in the dark
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING: Tested undiluted
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material): N/A

OTHER SPECIFICS: N/A

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: body weight variation did not exceed ±20% of the mean body weight at the start of treatment
- Fasting period before study: not specified
- Housing: individually housed in suspended solid floor polypropylene cages furnished with softwood flake bedding.
- Diet (e.g. ad libitum): free access to food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK)
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks of each animal were clipped free of hair.
- % coverage: Approximately 10% of total body surface
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi‑occluded with a piece of self‑adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- the treated skin and surrounding hair wiped with cotton wool moistened with dimethyl sulfoxide to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw (no correction made for purity)
- Constant volume or concentration used: 1.049 g/mL

Duration of exposure:

24h

Doses:

Limit test - 1000 mg/kg bw
Main 2000 mg/kg bw

No. of animals per sex per dose:

Limit test - 1
Main - 2

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted at approximately 0.5, 1, 2, 4, 6 hours and subsequently once daily for 14 days. Scoring and criteria were consistent with the Draize Draize. Individual bodyweight were recorded prior to application of the test item on Day -1 (before dosing) and on Days 0, 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

n/a

Results and discussion

Preliminary study:

No effect observed

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table  1. Dermal Reactions at Dose level 2000 mg/kg

Dose Level (mg/kg)

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0 Female

Erythema

2

2

1

0

?e

?e

?e

?e

?e

?e

?e

?e

?e

?e

Edema

1

1

1

1

?od

?od

?od

?od

?od

?od

?od

?od

?od

?od

Other

BlHd

BlHdTh

BlThSp

BlThSp

Sp

SpSk

SpSkSw

SpSkSw

SpSkSw

SpSkSw

SpSk SwSg

SpSk SwSg

SpSk SwSg

SpSkSg

3-0 Female

Erythema

1

2

2

2

?e

?e

?e

?e

?e

?e

?e

?e

?e

?e

Edema

1

1

1

1

?od

?od

?od

?od

?od

?od

?od

?od

?od

?od

Other

ThLf

ThBl

LfBlTh

LfBlTh

SpSw

SpSw

SpSw

SpSw

SpSw

SpSw

SpSw

SpSw

SpSwSk

SsSgSk

3-1 Female

Erythema

1

2

2

2

?e

?e

?e

?e

?e

?e

?e

?e

?e

?e

Edema

1

1

1

1

?od

?od

?od

?od

?od

?od

?od

?od

?od

?od

Other

ThLf

ThBlLf

ThBlLf

ThBlLf

SpSwSk

SpSwSk

SpSkSb

SdSb

SdSb

SdSb

SdSb

SbSpSk

SbSpSkSg

SkSpSg

0     = No reactions                                                        Hd  = Dermal hemorrhage                     

Th  = Thickening of the skin                                           ?e   = Dermal reactions prevented the accurate evaluation of erythema

Lf   = Loss of skin flexibility                                          ?od = Dermal reactions prevented the accurate evaluation of edema

Bl   = Blanching of the skin                                            Ss   = Small superficial scattered scabs                 

Sp  = Hardened brown colored scab

Sw  = Scab undulating

Sk  = Scab cracking

Sg  = Scab lifting to revel glossy skin

Sb  = Scab lifting at edges to reveal dried blood

Sd  = Scab lifting to at edges to reveal further deeper scabbing

Table  2. Individual Body Weight Changes at Dose level 2000 mg/kg

Dose Level (mg/kg)	Animal Number and Sex	Body Weight (g) at Day			Body Weight Change (g) During Week
		0	7	14	1	2
2000	2-0 Female	222	219	231	-3	12
	3-0 Female	229	232	232	3	0
	3-1 Female	232	229	232	-3	3

Table  3. Individual Necropsy Finding at Dose level 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
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in female Wistar (RccHan:WIST) strain rat. Applicant assessment indicates, under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Executive summary:

A study was performed according to OECD TG 402; Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test substance in the Wistar (RccHan:WIST)  strain rat.  Initial test was conducted with semi-occlusive application of undiluted test item at 1000 mg/kg bw to the clipped skin of one animinal. this is then followed by application of a single dose of the test item at a dose level of 2000 mg/kg body weight for a duration of 24 hour under semi-occluded condition and sequent observation for 14 days.

There was no mortality during the study. There were no signs of system toxicity or abnormalities on necropsy. Two animals treated at a dose level of 2000 mg/kg showed body weight loss with the remaining animal showing an expected gain in body weight during the first week. Two animals treated at a dose level of 2000 mg/kg showed expected gains in body weight with the remaining animal showing no gain in body weight during the second week. The animal treated at a dose level of 1000 mg/kg showed an expected gain in body weight during the observation period.. Signs of dermal irritation noted included very slight to well defined erythema and very slight edema, scattered areas of blanching over the treatment site, scattered areas of dermal hemorrhage over the treatment site, thickening of the skin, hardened light brown colored scabs, scab cracking, scab undulating, scab lifting to reveal glossy skin, scab lifting edge to reveal dried blood, scab lifting at edges to reveal further deeper scabbing, small superficial scattered scabs, glossy skin, loss of skin flexibility and loss of skin elasticity.  The dermal reactions prevented the accurate evaluation of erythema and edema at several time points.

Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in female Wistar (RccHan:WIST) strain rat. Applicant assessment indicates, under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.