RAL 3.0

Acute Toxicity: dermal

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Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

For the dermal route also an acute toxicity study is available (Elars Bioresearch Laboratories, Inc., 1981). The acute dermal LD50 for cryolite was greater than 2.1 g/kg bw under the specified conditions.

Adequacy of study:

key study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, unpublished report available, no restrictions, fully adequate for assessment

Cross-reference

Reason / purpose for cross-reference:

read-across source

Remarks:

The read-across can be performed because trisodium hexafluoroaluminate is component parts of RAL 3.0, and is the only component with possible negative effects for human health

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Remarks:

For the dermal route also an acute toxicity study is available (Elars Bioresearch Laboratories, Inc., 1981). The acute dermal LD50 for cryolite was greater than 2.1 g/kg bw under the specified conditions.

Adequacy of study:

weight of evidence

Study period:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study performed to a method equivalent to the relevant guidelines, well conducted, no limitations in reporting and fully adequate for assessment

Reason / purpose for cross-reference:

read-across source

Remarks:

The read-across can be performed because trisodium hexafluoroaluminate is component parts of RAL 3.0, and is the only component with possible negative effects for human health

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Determination of the potential dermal toxicity of the test material through percutaneous absorption in albino rabbits

GLP compliance:

yes

Specific details on test material used for the study:

The test material, a fine white powder in a clear glass Jar with black screw cap identified as Kryoclde® Insecticide (N.B. 84-146-2B), was received at Elars on May 28, 1981. Analytical data on the test material, as provided by the sponsor, included: concentration, 96% active Ingredient (sodium fluoalum~nate). The test material was stored at ambient temperature in Elars’ test material storage room.

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Twenty young adult New Zealand White rabbits (10 male, 10 female), purchased from L.I.T. Rabbitry, Whitehall, Montana, were approximately 2 months old upon receipt. Rabbits were randomized upon receipt at Elars according to SOP TA-3. They were identified individually by ear tag and corresponding cage tag and were housed in individual cages.
Throughout an 18 day acclimation period and during the study, rabbits were fed Purina Rabbit Chow and fresh water ad libitum. Rabbits weighed 2.2 to 3.3 kg at initiation of study.

Type of coverage:

occlusive

Vehicle:

other: physiological saline

Details on dermal exposure:

One dosage group of 2.1 g/kg body weight and an untreated control group were tested concurrently. Each group contained ten rabbits (five males and five females). 24 hours before application of test material, the rabbits were clipped free of hair with a clipper blade. The shaved area on each animal constituted at least 10 percent of the total body surface area. After the animals were shaved, they were returned to their stock cages to await testing on the following day. The 24-hour waiting period allowed recovery of the stratum corneum from the disturbance which accompanied the close-clipping procedure and permitted the healing of any microscopic abrasions possibly produced during the process.

Prior to application of test material, all rabbits were weighed to determine doses. The exposure sites of all rabbits were abraded by making four epidermal incisions, two parallel to the rabbits’ long axis and two perpendicular to the first abrasions. The abrasions, minor incisions through the stratum corneum, were not sufficiently deep to disturb the dermis or to produce bleeding.

The appropriate dose for each rabbit was calculated by multiplying the dosage (g/kg) times the weight of the rabbit (kg). This dose was weighed out on a Sartorius MP1264 Balance, moistened with physiological saline, and applied to 4" x 4" gauze sponges backed with plastic wrap to help prevent evaporation of the test material. The sponges and plastic wrap were taped to the shaved area of the rabbits’ ventralaspect with porous adhesive tape. The
entire trunk was then wrapped with elastic tape to prevent slippage of the patches. After application of the test material, the rabbits were returned to their cages

Duration of exposure:

24 hours

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent vehicle

Details on study design:

The control group was treated in a similar manner with physiological saline, but without test material.

The test material remained in contact with the skin for 24 hours. Behavioral reactions were observed and recorded during the contact period. At the end of 24 hours, the bandaging was removed and the skin wiped with gauze sponges to remove excess test material. Observations for mortality, local reactions, and behavioral abnormalities were continued twice daily for a total of 14 days following the skin applications. Initial, 7 and 14 day body weights were recorded. On the 14th day, all rabbits were killed and subjected to gross necropsy. Skin at the test site and tissues appearing abnormal were taken for histopathologic examination.

The tissues collected were fixed in 10% neutral buffered formalin. Afterwards, the tissues were trimmed, embedded in paraffin, sectioned at 4-5 microns, affixed to glass slides, and stained with hematoxylin and eosin. The histopathologic examination of the submitted tissues was conducted at Westpath Laboratories.

Statistics:

No data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 100 mg/kg bw

Mortality:

No mortality was observed

Clinical signs:

After bandage removal, all rabbits in the 2.1 g/kg test group had slightly red and swollen skin at the test site. Most rabbits in the test group appeared normal throughout the 14 day observation period, however, occasional soft stool, diarrhea, or ocular disdharge was observed in several animals. One rabbit was observed to have a head tilt on days 12-14 of the observation period. Torticollis as a result of otitis interna was not treatment related.

Control rabbits appeared normal after bandage removal. During the observation period, three animals exhibited soft stool, diarrhea, and/or ocular discharge. The remainder of the control animals appeared normal throughout this interval.

Body weight:

No effect on body weight was observed.

Gross pathology:

At gross necropsy, one rabbit in the 2.1 g/kg test group had pale, pitted kidneys; another rabbit had enlarged mesenteric lymph nodes. In the control group, one rabbit had diarrhea and another had a slightly enlarged spleen. All other test and control animals appeared normal at necropsy. These abnormalities observed were not considered test material related.

Eight of ten treated animals exhibited very slight to slight acanthosis, fibrosis, hyperkeratosis, and chronic dermal inflammation at the test site. No lesions were observed in the skin of control animals.

The kidneys of one treated rabbit had moderate inflammation and the mesenteric lymph node of another rabbit had a chronic inflammatory response. Congestion was observed in the spleen of one control animal. These lesions were considered to be naturally occurring and not related to the dermal application of the test material.

Interpretation of results:

GHS criteria not met

Remarks:

In accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for acute dermal toxicity based on the available data.

Conclusions:

The only hazardous component of RAL 3.0 is trisodium hexafluoroaluminate. It is present in amounts less than 1%. Because of this the preparation is not harmful.
No adverse health effects have been reported in RAL 3.0 product preparation workers or in those using this product.

Executive summary:

The acute dermal LD50 was greater than 2100 mg/kg bw.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Determination of the potential dermal toxicity of the test material through percutaneous absorption in albino rabbits.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

impurity

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): Cryolite
- Substance type: slighty coloured powder
- Analytical purity: 96.9%
- Composition of test material, percentage of components: Na 31%, Al 12.6%, F 53.3%
- Storage condition of test material: room temperature

Specific details on test material used for the study:

The test material, a fine white powder in a clear glass Jar with black screw cap identified as Kryoclde® Insecticide (N.B. 84-146-2B), was received at Elars on May 28, 1981. Analytical data on the test material, as provided by the sponsor, included: concentration, 96% active Ingredient (sodium fluoalum~nate). The test material was stored at ambient temperature in Elars’ test material storage room.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Twenty young adult New Zealand White rabbits (10 male, 10 female), purchased from L.I.T. Rabbitry, Whitehall, Montana, were approximately 2 months old upon receipt. Rabbits were randomized upon receipt at Elars according to SOP TA-3. They were identified individually by ear tag and corresponding cage tag and were housed in individual cages.
Throughout an 18 day acclimation period and during the study, rabbits were fed Purina Rabbit Chow and fresh water ad libitum. Rabbits weighed 2.2 to 3.3 kg at initiation of study.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other:

Remarks:

physiological saline

Details on dermal exposure:

One dosage group of 2.1 g/kg body weight and an untreated control group were tested concurrently. Each group contained ten rabbits (five males and five females). 24 hours before application of test material, the rabbits were clipped free of hair with a clipper blade. The shaved area on each animal constituted at least 10 percent of the total body surface area. After the animals were shaved, they were returned to their stock cages to await testing on the following day. The 24-hour waiting period allowed recovery of the stratum corneum from the disturbance which accompanied the close-clipping procedure and permitted the healing of any microscopic abrasions possibly produced during the process.

Prior to application of test material, all rabbits were weighed to determine doses. The exposure sites of all rabbits were abraded by making four epidermal incisions, two parallel to the rabbits’ long axis and two perpendicular to the first abrasions. The abrasions, minor incisions through the stratum corneum, were not sufficiently deep to disturb the dermis or to produce bleeding.

The appropriate dose for each rabbit was calculated by multiplying the dosage (g/kg) times the weight of the rabbit (kg). This dose was weighed out on a Sartorius MP1264 Balance, moistened with physiological saline, and applied to 4" x 4" gauze sponges backed with plastic wrap to help prevent evaporation of the test material. The sponges and plastic wrap were taped to the shaved area of the rabbits’ ventralaspect with porous adhesive tape. The
entire trunk was then wrapped with elastic tape to prevent slippage of the patches. After application of the test material, the rabbits were returned to their cages.

Duration of exposure:

24 h

Doses:

2.1 g/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent vehicle

Details on study design:

The control group was treated in a similar manner with physiological saline, but without test material.

The test material remained in contact with the skin for 24 hours. Behavioral reactions were observed and recorded during the contact period. At the end of 24 hours, the bandaging was removed and the skin wiped with gauze sponges to remove excess test material. Observations for mortality, local reactions, and behavioral abnormalities were continued twice daily for a total of 14 days following the skin applications. Initial, 7 and 14 day body weights were recorded. On the 14th day, all rabbits were killed and subjected to gross necropsy. Skin at the test site and tissues appearing abnormal were taken for histopathologic examination.

The tissues collected were fixed in 10% neutral buffered formalin. Afterwards, the tissues were trimmed, embedded in paraffin, sectioned at 4-5 microns, affixed to glass slides, and stained with hematoxylin and eosin. The histopathologic examination of the submitted tissues was conducted at Westpath Laboratories

Statistics:

No data

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 100 mg/kg bw

Mortality:

No mortality was observed.

Clinical signs:

After bandage removal, all rabbits in the 2.1 g/kg test group had slightly red and swollen skin at the test site. Most rabbits in the test group appeared normal throughout the 14 day observation period, however, occasional soft stool, diarrhea, or ocular disdharge was observed in several animals. One rabbit was observed to have a head tilt on days 12-14 of the observation period. Torticollis as a result of otitis interna was not treatment related.

Control rabbits appeared normal after bandage removal. During the observation period, three animals exhibited soft stool, diarrhea, and/or ocular discharge. The remainder of the control animals appeared normal throughout this interval.

Body weight:

No effect on body weight was observed.

Gross pathology:

At gross necropsy, one rabbit in the 2.1 g/kg test group had pale, pitted kidneys; another rabbit had enlarged mesenteric lymph nodes. In the control group, one rabbit had diarrhea and another had a slightly enlarged spleen. All other test and control animals appeared normal at necropsy. These abnormalities observed were not considered test material related.

Eight of ten treated animals exhibited very slight to slight acanthosis, fibrosis, hyperkeratosis, and chronic dermal inflammation at the test site. No lesions were observed in the skin of control animals.

The kidneys of one treated rabbit had moderate inflammation and the mesenteric lymph node of another rabbit had a chronic inflammatory response. Congestion was observed in the spleen of one control animal. These lesions were considered to be naturally occurring and not related to the dermal application of the test material.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

In accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for acute dermal toxicity based on the available data.

Conclusions:

The only hazardous component of RAL 3.0 is trisodium hexafluoroaluminate. It is present in amounts less than 1%. Because of this the preparation is not harmful.
No adverse health effects have been reported in RAL 3.0 product preparation workers or in those using this product.

Executive summary:

The acute dermal LD50 was greater than 2100 mg/kg bw.