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Toxicological information

Acute Toxicity: dermal

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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:
2005-09-27 to 2006-07-07
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study is conducted according to the current guidelines and under the conditions of GLP. As this study is being used for read-across, the reliability has been amended to reflect this. Read-across from potassium pentahydrogen bis(phosphate) to sodium dihydrogenorthophosphate is justified on the following basis. Both salts are monovalent inorganic phosphates, composed of a phosphate anion and an alkali metal cation. Both the Na+ and the K+ cation have a similar biological function and therefore orthophosphate salts of these types are not considered to differ in their systemic toxicity profile; differences arise in their local effects profile due to the increasing or decreasing acidity/alkalinity and buffering capacities of the substances. This has been shown not to have an effect on systemic toxicity. In addition, both salts have been shown to be of similar low toxicity in acute oral studies. These studies are supported by a number of acute oral studies on similar compounds which all show potassium and sodium orthophosphates to possess low systemic toxicity via the oral route (See section 7.2.1.) and therefore comparisons can be drawn to allow read-across for the acute dermal endpoint. Regarding the nature of the substances in question; inorganic, Molecular weight >100, the absorption through the dermal layer will be considerably less than via the gastro-intestinal tract (a route which has shown low systemic toxicity). This study is therefore deemed reliable for classification and labeling according to Regulation (EC) No 1272/2008 (EU CLP).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
GLP compliance:
yes
Test type:
fixed dose procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: PeKacid
- Lot No.: 0001
- Description: White crystalline powder
- Laboratory reference no.: 060214-3H
- Storeage: At room temperature
- Composition: The product is an inorganic phosphate salt. See methods table.
- pH 1 % water 2.2
- Solubility: Soluble in water (fully soluble)
- Stability: Test substance was expected to be stable for the duration of testing
- Expiration date: 2007-12-31

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA.
- Age at study initiation: 9 - 10 weeks (young adult)
- Weight at study initiation: Males 298 - 320 g; females 206 - 220 g.
- Housing: Singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent guide for the care and use of laboratory animals DHEW (NIH). Litter paper was placed beneath the case and was changed at least three times per week.
- Diet: Purina rodent chow #5012
- Water: Filtered tap water supplied ad libitum by automatic water dispenser.
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23 ºC
- Photoperiod (hrs dark / hrs light): 12-h light/dark cycle

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area and trunk.
- % coverage: Approximately 10 % (2 inches by 3 inches)
- Type of wrap if used: A gauze pad and 3 inch Durapore tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Test site was gently cleansed of any residual test substance.
- Time after start of exposure: After 24 h.

TEST MATERIAL
- Amount applied: 2000 mg/kg bw. Individual doese were calculated based on the initial body weights and concentration of the test mixture.
- Concentration: 90 % w/w
- For solids, paste formed: Yes the test substance was moistened with distiled water to acheive a dry paste.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination). Cage side observations for mortality, signs of gross toxicity and behavioural changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea and coma.
- Necropsy of survivors performed: Yes gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Statistics:
No data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: The test substance was applied as a 90 % w/w mixture in distilled water.
Mortality:
All animals survived.
Clinical signs:
All animals appeared healthy and active during the study. There were no signs of gross toxicity, dermal irritation, adverse pharmacologic effects or abnormal behaviour.
Body weight:
All animals gained body weight.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Other findings:
No data

Any other information on results incl. tables

Table 2. Individual body weights and doses:

Animal No.

Sex

Body weight

Dose*

Initial

Day 7

Day 14

9342

M

307

363

400

0.68

9343

M

320

348

388

0.71

9344

M

312

338

376

0.69

9345

M

298

345

390

0.66

9346

M

307

369

416

0.68

9347

F

212

227

239

0.47

9348

F

215

239

248

0.48

9349

F

214

243

253

0.48

9350

F

220

236

254

0.49

9351

F

206

242

261

0.46

* The test substance was applied as a 90 % w/w mixture in distilled water.

Table 3. Individual cage-side observations:

Animal No.

Findings

Day of occurrence

Males

9342 – 9346

Active and healthy

0 - 14

Females

9347 - 9351

Active and healthy

0 - 14

Table 4. Individual necroscopy observations:

Animal No.

Tissue

Findings

Males

9342 – 9346

All tissues and organs

No gross abnormalities

Females

9347 - 9351

All tissues and organs

No gross abnormalities

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the single dose acute dermal LD50 of PeKacid is greater than 2000 mg/kg bw in male and female rats.
This study is conducted according to the appropriate guidelines (EU AND US) and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for this endpoint.
In addition, this study is suitable to fulfill the requirements for classification and labelling according to Regulation (EC) No 1272/2008 (EU CLP).

Read-across from potassium pentahydrogen bis(phosphate) to disodium hydrogenorthophosphate is justified on the following basis:

Both salts are monovalent inorganic phosphates, composed of a phosphate anion and an alkali metal cation. Both the Na+ and the K+ cation have a similar biological function and therefore orthophosphate salts of these types are not considered to differ in their systemic toxicity profile; differences arise in their local effects profile due to the increasing or decreasing acidity/alkalinity and buffering capacities of the substances. This has been shown not to have an effect on systemic toxicity.
In addition, both salts have been shown to be of similar low toxicity in acute oral studies. These studies are supported by a number of acute oral studies on similar compounds which all show potassium and sodium orthophosphates to possess low systemic toxicity via the oral route (See section 7.2.1.) and therefore comparisons can be drawn to allow read-across for the acute dermal endpoint.
Regarding the nature of the substances in question; inorganic, Molecular weight >100, the absorption through the dermal layer will be considerably less than via the gastro-intestinal tract (a route which has shown low systemic toxicity).