Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 603-894-6 | CAS number: 135108-88-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Formaldehyde, polymer with benzenamine, hydrogenated (MPCA) is corrosive to skin and is a viscous, high boiling, low VP material therefore a repeat dose oral study was conducted to assess the effects of repeated administration. Effects on the kidney were observed from repeated oral exposure. There were no treatment-related effects at the low dose of 15 mg/kg/day and this dosage therefore represents the no-observed-effect level (NOAEL) in the rat for MPCA when administered orally for at least 28 days.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- other: 28 day repeat dose
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1995-1996
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study (GLP)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: A total of 38 male and 38 female healthy CD rats of Sprague-Dawley origin were received from Charles River (UK) Ltd., Margate, Kent, England on 27 September 1995.
- Age at study initiation: The rats were 28 _+ 1 days old
- Weight at study initiation: weight range of 68 to 87 g on arrival
- Housing: All rats were initially caged, as far as possible, in groups of five according to sex in metal cages with mesh floors.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: thirteen day acclimatisation period was allowed between delivery of the animals and start of treatmen
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22 °C
- Humidity (%): 34 to 62 % RH
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Details on oral exposure:
- The test substance was administered by oral gavage to rats of Groups 3 to 5 inclusive using a syringe
and rubber catheter at a dose volume of 10 ml/kg/day.
Control animals received the vehicle, PEG, or distilled water at the same dose volume
(10 ml/kg/day).
Each animal received a constant dosage based on its most recently recorded bodyweight. Animals
were treated once daily. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- MPCA was administered by oral gavage, once daily to three groups of rats for a minimum of twenty eight
consecutive days, at dosage levels of 15, 150 or 300 mg/kg/day . The test material was prepared
as suspensions in PEG (50% w/v aqueous polyethylene glycol 300) at concentrations of 1.5, 15 or
30 mg/ml and was administered at a dosage volume of 10 ml/kg/day. Vehicle control (Group 2)
received the vehicle (PEG) alone at the same dose volume (5 ml/kg/day) and a further group of
control animals (Group 1) received distilled water at 5 ml/kglday.
All rats of Groups 1, 3 and 4 (distilled water, 15 and 150 mg/kg/lday respectively) and five males and
five females from Group 2 and five males and four females of Group 5 (vehicle control and
500 mg/kg/day respectively) were killed following the four-week treatment period (Day 32, 10
November 1995). The remaining animals (five males and five females from Group 2 and two males
and four females of Group 5) were retained for a two-week recovery period, following which, they
were also killed (Day 46, 24 November 1995).
Bodyweights, food consumption and clinical observations were recorded during the study. Blood and
urine samples were taken from all rats shortly prior to termination following the four week treatment
and two-week recovery periods. All animals were killed and shortly examined macroscopically
specified tissues were then prepared for histopathological examination - Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
15 mg/kg/day
Basis:
nominal in diet - Remarks:
- Doses / Concentrations:
150 mg/kg/day
Basis:
nominal in diet - Remarks:
- Doses / Concentrations:
300 mg/kg/day
Basis:
nominal in diet - No. of animals per sex per dose:
- 5 males and 5 females per group
- Control animals:
- yes
- Details on study design:
- The study was designed to assess the systemic toxicity of MPCA to the rat when repeatedly
administered orally for a period of 4 weeks. Additional animals from the control and high dosage
groups were retained for a 2 week post-treatment observation period.
The albino rat was chosen as the test species as it has been shown to be a suitable model for this type
of study and is the species recommended in the test guidelines. The strain of rat used was chosen on
account of the availability of background data.
The rats were dosed orally as the test substance may be ingested accidentally.
The high dosage was selected on the basis of available toxicity data and a preliminary oral toxicity
investigation performed at this laboratory (Report number AIP 401960687). The high level dosage
of 300 mglkg was considered to be the highest dosage that could be tolerated for twenty-eight days
of dosing. The low and intermediate dose levels were selected on the basis of the key dosages
relative to EEC labelling requirement.
A total of 38 male and 38 female healthy CD rats of Sprague-Dawley origin were received from Charles River (UK) Ltd., Margate, Kent, England on 27 September 1995.
The rats were 28 +/- 1 days old, in a weight range of 68 to 87 g on arrival. A thirteen day
acclimatisation period was allowed between delivery of the animals and start of treatment.
All rats were initially caged, as far as possible, in groups of five according to sex in metal cages with
wire mesh floors.
A standard pelleted laboratory rodent diet (Special Diet Services Rat and Mouse Maintenance Diet)
and drinking water were provided ad libitum.
The batches of diet used for the study were analysed for nutrients, possible contaminants and microorganisms.
Results of the routine physical and chemical examination of drinking water at source, as conducted,
usually weekly by the supplier, were made available to Huntingdon Life Sciences Ltd. as quarterly
summaries.
The rats were housed in Building R17 Room 5. Animal room temperature was controlled in the range
19 to 22°C and relative humidity was controlled in the range 34 to 62% RH. These parameters were
continuously monitored using a Kent Clearspan MI05 7day chart recorder. Air exchange was
maintained at approximately 19 air changes per hour and lighting was controlled to provide 12 hours
artificial light (0700-1900 hours) in each 24-hour period.
The health status of all animals was monitored, by daily observation throughout the acclimatisation
period, to ensure that the rats selected for final assignment to the study were satisfactory.
Four days prior to the start of treatment each animal was weighed and seventy rats were randomly
allocated to five groups, two groups consisting of ten males and ten females and three groups
consisting of five males and five females. This allocation was carried out using a computer program,
so that the weight distribution within each group was similar and the initial group mean bodyweights
were approximately equalised.
Each rat was identified within each cage by ear-punch and individually by tail mark (tattoo).
Following the commencement of treatment spare animals were removed from the study. No further
investigations were performed on these animals.
The cages (each containing five rats) constituting each group were distributed in batteries in such'a
manner that possible environmental influences arising from their spatial distribution were equilibrated,
as far as possible, for all treatment.
MPCA was administered by oral gavage, once daily to three groups of rats for a minimum of twentyeight
consecutive days, at dosage levels of 15, 150 or 300 mg/kg/day . The test material was prepared
as suspensions in PEG (50% w/w aqueous polyethylene glycol 300) at concentrations of 1.5, 15 or
30 mglrnl and was administered at a dosage volume of 10 rnllkglday. Vehicle control (Group 2)
received the vehicle (PEG) alone at the same dose volume (5 mllkglday) and a further group of
control animals (Group 1) received distilled water at 5 rnllkglday.
All rats of Groups 1, 3 and 4 (distilled water, 15 and 150 mglkglday respectively) and five males and
five females from Group 2 and five males and four females of Group 5 (vehicle control and
500 mglkglday respectively) were killed following the four-week treatment period (Day 32, 10
November 1995). The remaining animals (five males and five females from Group 2 and two males
and four females of Group 5) were retained for a two-week recovery period, following which, they
were also killed (Day 46, 24 November 1995).
Bodyweights, food consumption and clinical observations were recorded during the study. Blood and
urine samples were taken from all rats shortly prior to termination following the four week treatment
and two-week recovery periods. All animals were killed and shortly examined macroscopically
specified tissues were then prepared for histopathological examiation. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Three male and two female rats from the high dosage group died during the treatment period. For high dosage rats, clinical signs included hunched posture, paddling of forepaws, unsteady gait, thin appearance, lethargy, soft faeces, wet urogenital region, distended stomach, partially closed eyes, noisy respiration and ungroomed appearance during the treatment period. Ungroomed appearance persisted for the first 5 days of the recovery period following which no toxicologically important clinical signs were noted.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Three male and two female rats from the high dosage group died during the treatment period. For high dosage rats, clinical signs included hunched posture, paddling of forepaws, unsteady gait, thin appearance, lethargy, soft faeces, wet urogenital region, distended stomach, partially closed eyes, noisy respiration and ungroomed appearance during the treatment period. Ungroomed appearance persisted for the first 5 days of the recovery period following which no toxicologically important clinical signs were noted.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Bodyweight gains were markedly lower than controls for male and females rats from the high dosage group during the treatment period. Gains were also lower for female rats of the intermediate dosage group.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Food consumption was lower than control for high dosage group males during the treatment period. During the recovery period, food consumption was similar for control and treated rats.
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- Food consumption was lower than control for high dosage group males during the treatment period. During the recovery period, food consumption was similar for control and treated rats.
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- Water consumption for high dosage group females was higher than control during Week 3. During the recovery period, water consumption was similar for control and treated rats.
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- There were no other findings for other parameters measured, including haematology that were considered to be related to treatment with MPCA.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- At the end of the treatment period higher glutamic-pyruvic transaminase (GPT) and glutarnicoxaloacetic transaminase (GOT) levels were recorded for high-dosage group rats. GOT levels were also slightly higher for intermediate dosage females. Urea nitrogen
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Lower urinary volumes for high dosage group rats and higher specific gravity was recorded for male rats of the high dosage groups, and also the intermediate dosage group, at the end of the treatment period. Higher protein levels
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- At the end of the 2-week recovery period, adrenal weights were higher than controls for high dosage group males.
- Gross pathological findings:
- effects observed, treatment-related
- Details on results:
- CLINICAL SIGNS
For high dosage rats, clinical signs included hunched posture, paddling of forepaws, unsteady gait, thin appearance, lethargy, soft faeces, wet urogenital region, distended stomach, partially closed eyes, noisy respiration and ungroomed appearance during the treatment period. Ungroomed appearance persisted for the first 5 days of the recovery period following which no toxicologically important clinical signs were noted.
MORTALITY
Three male and two female rats from the high dosage group died during the treatment period. Deaths
occurred from Day 8 to Day 30. Clinical signs seen among these animals prior to death included
ungroomed appearance, hunched posture, paddling of forepaws, unsteady gait, lethargy, soft faeces
and fur loss. Macroscopic examination revealed watery distension of the gastrointestinal tract, general
ungroomed appearance and brown stained fur. No treatment-related findings were seen at
microscopic examination. Due to the incidence and distribution of the deaths, and the clinical and
macroscopic observations, the deaths were considered to be treatment-related.
BODY WEIGHT AND WEIGHT GAIN
Bodyweight gains were markedly lower than controls for male and females rats from the high dosage
group during the treatment period. Gains were also lower for female rats of the intermediate dosage
group. The gains recorded for high dosage group rats during the recovery period were satisfactory.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Food consumption was lower than control for high dosage group males during the treatment period.
During the recovery period, food consumption was similar for control and treated rats.
FOOD EFFICIENCY
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Water consumption for high dosage group females was higher than control during Week 3. During
the recovery period, water consumption was similar for control and treated rats.
OPHTHALMOSCOPIC EXAMINATION
HAEMATOLOGY
CLINICAL CHEMISTRY
At the end of the treatment period higher glutamic-pyruvic transaminase (GPT) and glutarnicoxaloacetic
transaminase (GOT) levels were recorded for high-dosage group rats. GOT levels were
also slightly higher for intermediate dosage females. Urea nitrogen levels were higher and cholesterol
levels lower for high dosage females and triglyceride levels were higher for intermediate and high
dosage females. There were no treatment-related effects at the end of the recovery period.
URINALYSIS
Lower urinary volumes were recorded for high dosage group rats and consequently higher specific
gravity was recorded for male rats of the high dosage groups, and also the intermediate dosage group,
at the end of the treatment period. Higher protein levels were recorded for female rats.
At the end of the recovery period, high specific gravity and protein levels and low pH were recorded
for high dosage group male rats.
ORGAN WEIGHTS
Liver weights (bodyweight adjusted) were higher than control for intermediate and high dosage male
rats at the end of the treatment period. Adrenal weights were higher than control for high dosage
group males and females and kidney weights were higher than control for intermediate and high
dosage group male and female rats.
At the end of the 2-week recovery period, adrenal weights were higher than controls for high dosage
group males.
GROSS PATHOLOGY
At termination, pale and mottled kidneys, minimal adipose tissue, stained and badly groomed fur were
noted for the majority of high dosage group rats and watery contents of the small intestine was seen
for the high dosage males.
Following the 2 week recovery period, pale kidneys were noted for one high dosage group female
rat and badly groomed fur was noted for one high dosage group male rat. Fur loss was noted for one
male and all female rats for the high dosage group.
Treatment-related findings were reported in the kidneys, adrenals, liver and spleen.
Kidneys - Vacuolatiodfine vacuolation of the cortical tubular epithelium in male and female rats
receiving 150 or 300 mg/kg/day and in recovery male and female rats.
Basophilia and vacuolation of the cortical tubular epithelium and eosinophilic casts within cortical
tubules in male rats receiving 300 mglkglday and tubular dilation in male rats receiving 150 and
300 mg/kg/day. The basophilia and vacuolation and the tubular dilation were present in recovery
male rats.
Adrenals - Diffuse cortical hypertrophy in male and female rats receiving 300 mg/kg/day and in
recovery male and female rats.
Liver - Centrilobular hepatoctye enlargement in male rats receiving 150 or 300 mg/kg/day and in
recovery male rats.
Spleen - Lymphocytolysis was reported in occasional male rats receiving 150 or 300 mg/kg/day and
female rats receiving 300 mg/kg/day. It was present in recovery male rats. This findings is
considered of minor toxicological importance.
OTHER FINDINGS
There were no other findings for other parameters measured, including haematology that were
considered to be related to treatment with MPCA.
The only findings of note for control animals receiving the vehicle, PEG 300 in comparison to
distilled water controls were lower bodyweight gains for females, higher water consumption for
males, higher urinary specific gravity (males and females), lower urinary volume (females) and lower
urinary pH (males). All other differences from vehicle control rats in comparison to distilled water
controls were considered incidental. There findings were not considered to have affected the
evaluation of findings related to treatment with MPCA. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 15 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 150 mg/kg bw/day (nominal)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Conclusions:
- The treatment-related effects seen at the high and intermediate dosage groups, in particular in the kidney, were considered to be adverse and represent the potential of the test substance to cause serious damage to health. According to Commission Directive 93/21/EEC the R48 (harmful) risk
phase is required for Formaldehyde, polymer with benzenamine, hydrogenated (MPCA).
There were no treatment-related effects at the low dosage of 15 mg/kg/day and this dosage therefore represents the no-observed-effect level (NOEL) in the rat for MPCA when administered orally for at least 28 days. - Executive summary:
The treatment-related effects seen at the high and intermediate dosage groups, in particular in the kidney, were considered to be adverse and represent the potential of the test substance to cause serious damage to health. According to Commission Directive 93/21/EEC the R48 (harmful) risk
phase is required for MPCA (Formaldehyde, polymer with benzenamine, hydrogenated).
There were no treatment-related effects at the low dosage of 15 mg/kg/day and this dosage therefore represents the no-observed-effect level (NOEL) in the rat for MPCA when administered orally for at least 28 days.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 15 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Klimisch study 1. According to GLP and OECD Guideline 407.
- Organ:
- kidney
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Formaldehyde, polymer with benzenamine, hydrogenated (MPCA) is corrosive to skin and is a viscous, high boiling, low VP material therefore a repeat dose oral study was conducted to assess the effects of repeated administration. Effects on the kidney were observed from repeated oral exposure. There were no treatment-related effects at the low dose of 15 mg/kg/day and this dosage therefore represents the no-observed-effect level (NOEL) in the rat for MPCA when administered orally for at least 28 days.
Justification for selection of repeated dose toxicity via oral
route - systemic effects endpoint:
only one study available
Justification for classification or non-classification
The treatment-related effects seen at the high (300 mg/kg bw) and intermediate (150 mg/kg bw) dosage groups in the 28 -day oral toxicity study, in particular in the kidney, were considered to be adverse and represent the potential of the test substance to cause serious damage to health. The kidney is considered to be a target organ.
Thus, according to EU Regulation 1272/2008 classification for specific target organ toxicity-repeated exposure Category 2 (STOT RE 2; H373) is applicable for the registered substance.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.