Registration Dossier

Administrative data

Description of key information

Nitroethane was not irritating to the skin in the Draize test.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
We have only an in vivo study, no in vitro study. That is why we are using this in vivo study, in agreement with the requirements for this endpoint.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 Nov 1980 - 20 Nov 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted comparable to test guidelines and in accordance with GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
rabbits were tested on intact and abraded skin
GLP compliance:
yes
Species:
rabbit
Strain:
other: albino
Details on test animals and environmental conditions:
The primary dermal irritation test for P-1355 was conducted in six albino rabbits weighing 2.1+/-0.1 kg.
Type of coverage:
occlusive
Preparation of test site:
other: Test site was shaved and test material was applied on intact and abraded skin.
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hour
Observation period:
The skin reactions were scored immediately (24 h) and at the end of 72 hr (48 h after the first scoring).
Number of animals:
6
Details on study design:
The skin from the back area of each animal was clipped free of hair. The prepared skin site left of the middorsal line on each rabbit was left intact while the skin on the right side was abraded at two separate places by making minor epidermal incisions in a tic tac toe pattern with a blunt hypodermic needle. The abrasions were minor incisions through the stratum corneum, but not deep enough to disturb the derma or produce bleeding. A total offour sites were treated in each rabbit, two intact and two abraded, with the test material.A 0.5 ml of P-1355, was applied to each site and covered with a moistened gauze pad. The entire trunk was then wrapped with a rubberized impervious cloth and a flexible stainless steel wire screen held in place by tape. After 24 h exposure, the bindings and the patches were removed and the treated skin sites were gently cleaned. The skin reactions were scored immediately (24 h) and at the end of 72 hr (48 h after the first scoring).
Irritation parameter:
overall irritation score
Remarks:
Edema and Erythema were scored.
Basis:
mean
Time point:
24 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: The maximum score 1 for erythema and edema was found on only one animal and fully reversed within 72 hours.
Irritant / corrosive response data:
At 24 h the compound produced mild erythema and edema (each scored as 1) on the abraded skin sites of one rabbit (#479), the treated skin sites in the other rabbits were normal. The average skin irritation score for the six rabbits for the two observation periods was 0.1.
Other effects:
No additional information available.

No additional information available.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Nitroethane (P-1355) was nonirritating to the skin.
Executive summary:

The skin irritation potential of nitroethane was examined. Of the six rabbits tested, there was no irritation observed on intact skin. On abraded skin, only one had erythema and edema observed at the abraded application site at the end of the exposure period. None of the rabbits exhibited irritation 48 hours later. Thus using the criteria of OECD Guideline 404 of testing only intact skin, nitroethane (P-1355) produced no irritation in rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
We have only an in vivo study, no in vitro study. That is why we are using this in vivo study, in agreement with the requirements for this endpoint.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 January 1989 - 3 February 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guidelines but was conducted according to GLPs and the report contains sufficient data for interpretation of study results.
Qualifier:
equivalent or similar to
Guideline:
other: Federal Hazardous Substances Act Regulations (16 CFR Part 1500)
Deviations:
yes
Remarks:
Since a positive response was observed in 2 of 6 rabbits, the guideline indicates the test should be repeated. The test was not repeated.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Young adult New Zealand White rabbits (Ace Animals, Inc., Boyertown, PA) were acclimated to the laboratory environment for at least five days prior to study initiation. They were observed daily during the acclimation period to assure their suitability as test animals. All housing and care conformed to the standards establisted in the "Guide for the Care and Use of Laboratory Animals" DHEW Publication No. (NIH) 85-23. Each animal was housed in a wire mesh cage and identified with an ear tag and color coded cage card. NIH 09 Rabbit Ration (Zeigler Brothers, Inc., Gardners, PA) and fresh tap water were selected randomly from the acclimated colony and assigned to the test group. The eyes of each rabbit were examined with sodium fluorescein and a slit light equipped with a cobalt blue filter prior to dosing to verify the absence of pre-existing ocular lesions.
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1 ml was instilled into the right eye of each rabbit.
Duration of treatment / exposure:
According to the report the test material is allowed to remain on the eye till the study ends
Observation period (in vivo):
Primary eye irritation was evaluated 24, 48 and 72 hours after the test material was administered.
Number of animals or in vitro replicates:
6 rabbits
Details on study design:
Eyes were examined with sodium fluorescein and a slit light equipped with a cobalt blue filter prior to dosing to verify the absence of pre-existing ocular lesions. The test material (0.1 ml) was instilled into the right conjunctival sac of each rabbit and the lids were held together for one second and released. The animals were observed twice daily for mortality at least 5 hours apart. Primary eye irritation was evaluated 24, 48 and 72 hours after the test material was administered. The cornea, iris and conjunctiva were scored separately according to the method of Draize. The total maximum score was 110.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
6.2
Max. score:
18
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
4.2
Max. score:
9
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
1
Max. score:
2
Reversibility:
not specified
Irritant / corrosive response data:
According to the report, 2 of 6 rabbits exhibited corneal irritation 24 hours after application. One of 6 rabbits exhibited iris and conjunctiva irritation 24 hrs after application. There was no evidence of corneal, iris or conjunctival irritation after 72 hours.
Other effects:
The untreated eyes of four animals exhibited diffuse areas of corneal opacity during the study.

Table 1 Summary of Primary Eye Irritation Scores

 Number of        Mean Score +/- Standard Deviation after Test Article Instillation
 Animals Dosed  24 hours  48 hours  72 hours
 6  6.2 + 6.4  4.2 + 3.1  1.0 + 1.1
 Individual Draize Values  4, 18, 2, 9, 2, 2  4, 6, 4, 9, 0, 2  2, 2, 0, 2, 0, 0

According to the classification used, the two most severe readings would equate to moderately and mildly irritating. In the case of the rabbit with a score of 18, the cornea opacity and area was rated a 1 and 1, respectively. Iris was rated a 1. Conjunctival rednes, chemosis, and discharge were 2, 1 and 1, respectively. By 48 hours, the only positive symptoms in this rabbit was conjunctival redness and chemosis which were 2 and 1, respectively. Thus the observed effects were considered to be minimal even though the rating scheme would classify the effect as moderate.

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Based on the results of this test, nitroethane is equivocal as a primary eye irritant. The maximum average eye irritation score was 6.2 at 24 hours after dose administration. Based on this score, nitroethane is considered mildly irritating to rabbit eyes.
Executive summary:

The eye irritation potential was evaluated using the U.S. Federal Hazardous Substances Act Regulation (16 CFR Part 1500). Based on the results of this test, nitroethane is equivocal as a primary eye irritant. The maximum average eye irritation score was 6.2 at 24 hours after dose administration. Based on this score, nitroethane is considered mildly irritating to rabbit eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Dermal

The skin irritation potential of nitroethane was examined in three studies. In one study, the test material was slightly irritating to the skin in the Draize test. In the remaining studies, the material caused no irritation to intact skin but caused very slight redness and scab formation to abraded skin.

Eye

Three eye irritation studies have been conducted on nitroethane. In one study, slight pain was noted following application. In the three studies, very slight to slight eye irritation was observed which essentially subsided within 24 hours in two studies and minimal irritation in the third study.


Justification for selection of skin irritation / corrosion endpoint:
The study was conducted comparable to test guidelines and in accordance with GLP

Justification for selection of eye irritation endpoint:
The study was not conducted according to guidelines but was conducted according to GLPs and the report contains sufficient data for interpretation of study results.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Nitroethane was not irritating when applied to intact skin and therefore not classifiable under GHS

Nitroethane was only slightly irritating to the eyes and not classifiable under GHS.