Silver docosanoate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Species: Rat, Wistar strain Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC)
- Number of animals: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
- Age and body weight: Young adult animals (approx. 8-9 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
- A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

single dose: 2000mg/kg (10ml/kg)

No. of animals per sex per dose:

3

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

dissolved

Remarks on result:

other: No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Mortality:

No mortality occurred.

Clinical signs:

Hunched posture and/or piloerection were noted in all animals on Day 1.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Gross pathology:

One animal showed pelvic dilation. No further abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of CH03220 in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, CH03220 does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Executive summary:

Assessment of acute oral toxicity with CH03220 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in:
OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"
Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method" EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"
JMAFF guidelines (2000) including the most recent partial revisions.

CH03220 was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.
Hunched posture and/or piloerection were noted in all animals on Day 1.

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

One animal showed pelvic dilation. No further abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of CH03220 in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, CH03220 does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the:

• -  Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United

  Nations (2011),

• -  Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and

  mixtures

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

Testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. Substance is in solid phase - non-powder form. The low dustiness justifies the low relevance of the inhalation pathway. Therefore, dermal is therefore the second most relevant exposure route.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines 2000 (incl. most recent revisions)

Deviations:

no

Principles of method if other than guideline:

Deviations from the minimum level of relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations.
The study integrity was not adversely affected by the deviation.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles RIver Deutschalnd, Sulzfeld, Germany
- Females are nulliparous and non-pregnant
- Age: approx 10 weeks
- Body weight: variation did not exceed +/- 20% of the sex mean
- Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0oC (actual range: 19.8 – 23.5oC), a relative humidity of 40-70% (actual range: 36 - 66%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Type of coverage:

occlusive

Vehicle:

corn oil

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, * successively covered with aluminum foil and Coban elastic bandage . A piece of Micropore tape* was additionally used for fixation of the bandages in females only.

Duration of exposure:

24h

Doses:

2000 mg/kg (10 mL/kg)
single dosage on day 1

No. of animals per sex per dose:

5 (5 males and 5 females)

Details on study design:

- Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany). Free access to tap water.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

dissolved

Mortality:

No mortality occurred.

Clinical signs:

Chromodacryorrhoea was noted in two males and two females on Day 1.
Scales were seen in the treated skin-area of one male in the second week of the study.

Body weight:

The changes noted in body weight gain in males and females were within the range expected for rats
used in this type of study and were therefore considered not indicative of toxicity.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of CH03220 in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

Assessment of acute dermal toxicity with CH03220 in the rat.

The study was carried out based on the guidelines described in:
OECD No.402 (1987) "Acute Dermal Toxicity"
Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)" EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity"

JMAFF Guidelines (2000), including the most recent revisions.

CH03220 was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Chromodacryorrhoea was noted in two males and two females on Day 1.

Scales were seen in the treated skin-area of one male in the second week of the study.

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of CH03220 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, CH03220 does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United

Nations (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and

mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

No acute toxicity is observed for the oral and dermal route. Testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. Substance is in solid phase - non-powder form. Therefore, dermal is the second most relevant exposure route.